Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interfe... more Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lungmetastases in a syngeneic B16F10LacZ lungmetastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can
DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specifi... more DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specific cytotoxic T cells into tumours. Cancer cells upregulate phosphatidylserine (PS) on the cell surface as a mechanism to induce an immunosuppressive microenvironment. Development of anti-PS targeting antibodies have highlighted the ability of a PS-blockade to enhance tumour control by T cells by releasing immunosuppression. Here, C57BL/6 mice were implanted with HPV16 E7 target-expressing C3 tumours and subjected to low dose intermittent cyclophosphamide (CPA) in combination with DPX-R9F treatment targeting an E7 antigen with and without anti-PS and/or anti-PD-1 targeting antibodies. Immune responses were assessed via IFN-γ ELISPOT assay and the tumour microenvironment was further analyzed using RT-qPCR. We show that the combination of DPX-R9F and PS-targeting antibodies with and without anti-PD-1 demonstrated increased efficacy compared to untreated controls. All treatments containing DP...
ABSTRACT The small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a ... more ABSTRACT The small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a transmembrane protein that is poorly accessible by antibodies on the virion but has an ectodomain (SHe) that is accessible and expressed on infected cells. The SHe from RSV strain A has been formulated in DPX, a unique delivery platform containing an adjuvant, and is being evaluated as an RSV vaccine candidate. The proposed mechanism of protection is the immune-mediated clearance of infected cells rather than neutralization of the virion. Our phase I clinical trial data clearly showed that vaccination resulted in robust antibody responses, but it was unclear if these immune responses have any correlation to immune responses to natural infection with RSV. Therefore, we embarked on this study to examine these immune responses in older adults with confirmed RSV infection. We compared vaccine-induced (DPX-RSV(A)) immune responses from participants in a Phase 1 clinical trial to paired acute and convalescent titers from older adults with symptomatic laboratory-confirmed RSV infection. Serum samples were tested for anti-SHe IgG titers and the isotypes determined. T cell responses were evaluated by IFN-γ ELISPOT. Anti-SHe titers were detected in 8 of 42 (19%) in the acute phase and 16 of 42 (38%) of convalescent serum samples. IgG1, IgG3, and IgA were the prevalent isotypes generated by both vaccination and infection. Antigen-specific T cell responses were detected in 9 of 16 (56%) of vaccinated participants. Depletion of CD4+ but not CD8+ T cells abrogated the IFN-γ ELISPOT response supporting the involvement of CD4+ T cells in the immune response to vaccination. The data showed that an immune response like that induced by DPX-RSV(A) could be seen in a subset of participants with confirmed RSV infection. These findings show that older adults with clinically significant infection as well as vaccinated adults generate a humoral response to SHe. The induction of both SHe-specific antibody and cellular responses support further clinical development of the DPX-RSV(A) vaccine.
6075 Background: DPX-Survivac is a novel T-cell activating therapy designed to elicit an effectiv... more 6075 Background: DPX-Survivac is a novel T-cell activating therapy designed to elicit an effective immune response against survivin expressing tumors. Its unique mechanism of action (MOA) facilitates active and sustained uptake of target peptides by APC at the injection site. APCs subsequently present the antigen in local lymph nodes generating survivin-specific T cells that traffic to distant tumor sites and elicit effective tumor cell death. DPX-Survivac is used in combination with intermittent low dose CPA which acts as an immunomodulator of T-cell responses. Methods: The study enrolled 22 patients with recurrent, advanced platinum-sensitive and -resistant ovarian cancer. Patients received 2 subcutaneous injections of DPX-Survivac 3 weeks apart and every 8 weeks thereafter, and intermittent low dose CPA for up to 1 year. Paired tumor biopsies were performed prior to treatment and on treatment. Primary endpoints were ORR, DCR and safety. Secondary endpoints include cell mediated i...
3030 Background: Survivin, a protein involved in regulation of apoptosis, is highly expressed in ... more 3030 Background: Survivin, a protein involved in regulation of apoptosis, is highly expressed in many tumor types and has reported prognostic value. DPX-Survivac is a cocktail of survivin HLA class I peptides (A1, A2, A3, A24 and B7) formulated in the novel adjuvanting vaccine platform DepoVax. A phase I study examined the safety and immune potency of DPX-Survivac in combination with cyclophosphamide in ovarian cancer patients. Methods: 18 of 19 advanced ovarian cancer patients treated with platinum chemotherapy and showing no disease progression completed their vaccine therapy. Cohort A (6 pts) received three 0.5 mL vaccine injections 3 weeks apart; cohorts B and C (6 pts each) received three 0.1 mL or 0.5 mL vaccine injections in combination with metronomic low dose oral cyclophosphamide. Adverse events were assessed using CTCAE v4.0. Blood was collected to study immune function (MDSCs, T regs and B cells) and vaccine-induced T cell immunity (ELISpot, tetramer analysis and multi-p...
2588 Background: To increase the efficacy of peptide cancer vaccines, we developed a novel vaccin... more 2588 Background: To increase the efficacy of peptide cancer vaccines, we developed a novel vaccine platform called DepoVax, an adjuvanted water-free depot formulation with the ability to generate enhanced immune responses. Naturally processed HLA-A2 restricted peptides that are selectively presented by breast, ovarian and prostate cancer cell lines, but not by normal HLA-A2+ cells, were used as antigens with a proprietary adjuvant and a T helper peptide epitope to create a therapeutic cancer vaccine, DPX-0907. Methods: A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose volume cohorts in a three immunization clinical protocol. Results: DPX-0907 proved to be safe with no serious adverse effects related to the vaccine reported. Of those evaluable for immunogenicity, all breast cancer p...
6 Background: Survivin has emerged as an attractive target for T cell-based immunotherapy because... more 6 Background: Survivin has emerged as an attractive target for T cell-based immunotherapy because of its essential role in tumor biology and its tumor-specific expression in multiple tumor types. DPX-Survivac is a novel T cell immunotherapy that uses the DPX platform to elicit strong and sustained survivin-specific T cell responses against tumor cells. DPX is designed to extend the duration and robustness of targeted immune responses by requiring active uptake of antigens by antigen presenting cells at the injection site. DPX-Survivac incorporating survivin targets within the DPX platform is therefore a relevant approach for treatment of survivin-expressing cancers to generate strong T cell responses that infiltrate tumors and result in measurable anti-tumor responses. Methods: 121 patients with platinum sensitive or resistant, advanced ovarian, fallopian tube or peritoneal cancer were treated with DPX-Survivac with or without drug combinations. Data from 3 different clinical trials...
e17550Background: DPX-Survivac is a novel T cell activating therapy containing a mix of HLA class... more e17550Background: DPX-Survivac is a novel T cell activating therapy containing a mix of HLA class I peptides designed to evoke a T cell response against survivin, optimized for cytotoxic activity w...
e14578Background: Survivin is strongly expressed in tumors of about 60% of diffuse large B-cell l... more e14578Background: Survivin is strongly expressed in tumors of about 60% of diffuse large B-cell lymphoma (DLBCL) patients. DPX-Survivac contains survivin HLA class I peptides in a novel formulation...
5576 Background: DPX-Survivac is a novel T cell activating therapy designed to elicit an effectiv... more 5576 Background: DPX-Survivac is a novel T cell activating therapy designed to elicit an effective immune response against recurrent ovarian cancers that express the survivin protein. The survivin specific T cells induced by DPX-Survivac can infiltrate the tumors and are associated with clinical responses. It is likely that achieving an anti-tumor effect requires a favorable ratio of T cells to tumor cells. Epacadostat (E) is an IDO1 enzyme inhibitor that may enhance effector T cell proliferation, shifting the tumor microenvironment (TME) away from an immunosuppressive state toward one supporting productive immune response. Methods: Recurrent ovarian cancer patients with advanced and metastatic progressive disease were treated with DPX-Survivac, intermittent low dose CPA with or without E. In the Phase 1b, 53 subjects were enrolled to receive DPX-Survivac, low dose CPA and E BID. In the Phase 2, 12 subjects were randomized to receive DPX-Survivac and low dose CPA with or without E. ...
Neoantigens are emerging targets for personalized cancer vaccines that provide patient specific c... more Neoantigens are emerging targets for personalized cancer vaccines that provide patient specific cancer immunotherapies. Many algorithms have been developed to select the most immunogenic neoantigens to include, however not all neoantigens chosen will generate equivalent immune responses, nor may they induce effective anti-tumour activity. To maximize immunological activity, selected peptides should be delivered simultaneously in a formulation that can stimulate potent, sustained immune responses to many different peptides. The DepoVaxTM platform is an oil-based system that uses lipids to incorporate many different types of antigens and adjuvants into a single formulation. Using a set of neoantigens identified from murine B16-F10 melanoma, we optimized a DepoVax formulation method that allows us to incorporate up to 14 neoantigens with a polynucleotide based adjuvant in a single formulation. These selected neoantigens irrespective of their solubility and hydrophobicity were formulated in DepoVax with the contents completely soluble in oil. C57BL/6 mice were vaccinated with 14 synthetic long peptide neoantigens (each 27 amino acids in length) prepared in DepoVax or in an aqueous formulation containing poly ICLC adjuvant. The immune responses were assessed eight days later by IFN-γ ELISPOT using splenocytes. Several of the peptides generated strong immune responses that were significantly higher in mice vaccinated with the DepoVax formulation compared to the aqueous formulation. To assess the contribution of CD8+ and CD4+ T cell responses, splenocytes from vaccinated mice were stimulated with an immunogenic peptide and intracellular IFN-γ/TNF-α producing CD8+ or CD4+ T cells were detected by flow cytometry. The highest production of TNF-α was detected by CD8+ T cells. Biological activity of the vaccines was assessed after one month storage at -20, 5 and 25 °C by IFN-γ ELISPOT assay; no significant difference was detected compared to the initial results. Analytical characterization of 14 peptides in DepoVax carried out using high-performance liquid chromatography (RP-HPLC), detected no significant chemical modifications or degradation of peptides after storage at -20 °C for up to 3 months compared to the initial results. These results demonstrate that the DepoVax platform can incorporate at least 14 neoantigens in a single formulation. Neoantigens formulated in DepoVax are stable for at least 3 months and our manufacturing method can incorporate peptides with a wide range of physical and chemical characteristics. This formulation generates strong CD8+ T cell responses, in excess of those induced by an aqueous formulation. The DepoVax platform is a promising solution to inducing robust immune responses to multiple neoantigens in a single formulation. Citation Format: Valarmathy Kaliaperumal, Genevieve Weir, Rajkannan Rajagopalan, Arthvan Sharma, Heather Torrey, Alecia MacKay, Ava Vila-Leahey, Cynthia Tram, Andrea Penwell, Leeladhar Sammatur, Marianne Stanford. A novel delivery platform containing up to 14 neoantigens can induce robust immune responses in a single formulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1726.
3072 Background: Survivin is important in apoptosis, proliferation, and angiogenesis. High expres... more 3072 Background: Survivin is important in apoptosis, proliferation, and angiogenesis. High expression has been linked to progression and drug resistance. DPX-Survivac vaccine (DPX) contains a mix of survivin HLA class I peptides designed to evoke a cytotoxic T cell response against survivin. This trial reports the safety and immune response profiles of DPX in combination with metronomic low dose oral cyclophosphamide (CPA) in ovarian cancer (OC). Methods: 40 Stage IIc-IV OC patients with no evidence of disease progression post-platinum chemotherapy were enrolled. Adverse events and dose limiting toxicities (DLT) were defined by CTCAE v4.03. Immune correlates (MDSCs; T regs; B cells) and vaccine induced T cell immunity (ELISpot; tetramer analysis) was assessed in purified PBMC and blood. Clinical response was assessed by CT and CA125. Results: 34/40 pts had an HLA match with the vaccine. Local injection site reactions (ISR) were the main DLT with 2 grade 3 skin ulcerations in cohort C. One hematological gr...
Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interfe... more Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lungmetastases in a syngeneic B16F10LacZ lungmetastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can
DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specifi... more DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specific cytotoxic T cells into tumours. Cancer cells upregulate phosphatidylserine (PS) on the cell surface as a mechanism to induce an immunosuppressive microenvironment. Development of anti-PS targeting antibodies have highlighted the ability of a PS-blockade to enhance tumour control by T cells by releasing immunosuppression. Here, C57BL/6 mice were implanted with HPV16 E7 target-expressing C3 tumours and subjected to low dose intermittent cyclophosphamide (CPA) in combination with DPX-R9F treatment targeting an E7 antigen with and without anti-PS and/or anti-PD-1 targeting antibodies. Immune responses were assessed via IFN-γ ELISPOT assay and the tumour microenvironment was further analyzed using RT-qPCR. We show that the combination of DPX-R9F and PS-targeting antibodies with and without anti-PD-1 demonstrated increased efficacy compared to untreated controls. All treatments containing DP...
ABSTRACT The small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a ... more ABSTRACT The small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a transmembrane protein that is poorly accessible by antibodies on the virion but has an ectodomain (SHe) that is accessible and expressed on infected cells. The SHe from RSV strain A has been formulated in DPX, a unique delivery platform containing an adjuvant, and is being evaluated as an RSV vaccine candidate. The proposed mechanism of protection is the immune-mediated clearance of infected cells rather than neutralization of the virion. Our phase I clinical trial data clearly showed that vaccination resulted in robust antibody responses, but it was unclear if these immune responses have any correlation to immune responses to natural infection with RSV. Therefore, we embarked on this study to examine these immune responses in older adults with confirmed RSV infection. We compared vaccine-induced (DPX-RSV(A)) immune responses from participants in a Phase 1 clinical trial to paired acute and convalescent titers from older adults with symptomatic laboratory-confirmed RSV infection. Serum samples were tested for anti-SHe IgG titers and the isotypes determined. T cell responses were evaluated by IFN-γ ELISPOT. Anti-SHe titers were detected in 8 of 42 (19%) in the acute phase and 16 of 42 (38%) of convalescent serum samples. IgG1, IgG3, and IgA were the prevalent isotypes generated by both vaccination and infection. Antigen-specific T cell responses were detected in 9 of 16 (56%) of vaccinated participants. Depletion of CD4+ but not CD8+ T cells abrogated the IFN-γ ELISPOT response supporting the involvement of CD4+ T cells in the immune response to vaccination. The data showed that an immune response like that induced by DPX-RSV(A) could be seen in a subset of participants with confirmed RSV infection. These findings show that older adults with clinically significant infection as well as vaccinated adults generate a humoral response to SHe. The induction of both SHe-specific antibody and cellular responses support further clinical development of the DPX-RSV(A) vaccine.
6075 Background: DPX-Survivac is a novel T-cell activating therapy designed to elicit an effectiv... more 6075 Background: DPX-Survivac is a novel T-cell activating therapy designed to elicit an effective immune response against survivin expressing tumors. Its unique mechanism of action (MOA) facilitates active and sustained uptake of target peptides by APC at the injection site. APCs subsequently present the antigen in local lymph nodes generating survivin-specific T cells that traffic to distant tumor sites and elicit effective tumor cell death. DPX-Survivac is used in combination with intermittent low dose CPA which acts as an immunomodulator of T-cell responses. Methods: The study enrolled 22 patients with recurrent, advanced platinum-sensitive and -resistant ovarian cancer. Patients received 2 subcutaneous injections of DPX-Survivac 3 weeks apart and every 8 weeks thereafter, and intermittent low dose CPA for up to 1 year. Paired tumor biopsies were performed prior to treatment and on treatment. Primary endpoints were ORR, DCR and safety. Secondary endpoints include cell mediated i...
3030 Background: Survivin, a protein involved in regulation of apoptosis, is highly expressed in ... more 3030 Background: Survivin, a protein involved in regulation of apoptosis, is highly expressed in many tumor types and has reported prognostic value. DPX-Survivac is a cocktail of survivin HLA class I peptides (A1, A2, A3, A24 and B7) formulated in the novel adjuvanting vaccine platform DepoVax. A phase I study examined the safety and immune potency of DPX-Survivac in combination with cyclophosphamide in ovarian cancer patients. Methods: 18 of 19 advanced ovarian cancer patients treated with platinum chemotherapy and showing no disease progression completed their vaccine therapy. Cohort A (6 pts) received three 0.5 mL vaccine injections 3 weeks apart; cohorts B and C (6 pts each) received three 0.1 mL or 0.5 mL vaccine injections in combination with metronomic low dose oral cyclophosphamide. Adverse events were assessed using CTCAE v4.0. Blood was collected to study immune function (MDSCs, T regs and B cells) and vaccine-induced T cell immunity (ELISpot, tetramer analysis and multi-p...
2588 Background: To increase the efficacy of peptide cancer vaccines, we developed a novel vaccin... more 2588 Background: To increase the efficacy of peptide cancer vaccines, we developed a novel vaccine platform called DepoVax, an adjuvanted water-free depot formulation with the ability to generate enhanced immune responses. Naturally processed HLA-A2 restricted peptides that are selectively presented by breast, ovarian and prostate cancer cell lines, but not by normal HLA-A2+ cells, were used as antigens with a proprietary adjuvant and a T helper peptide epitope to create a therapeutic cancer vaccine, DPX-0907. Methods: A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose volume cohorts in a three immunization clinical protocol. Results: DPX-0907 proved to be safe with no serious adverse effects related to the vaccine reported. Of those evaluable for immunogenicity, all breast cancer p...
6 Background: Survivin has emerged as an attractive target for T cell-based immunotherapy because... more 6 Background: Survivin has emerged as an attractive target for T cell-based immunotherapy because of its essential role in tumor biology and its tumor-specific expression in multiple tumor types. DPX-Survivac is a novel T cell immunotherapy that uses the DPX platform to elicit strong and sustained survivin-specific T cell responses against tumor cells. DPX is designed to extend the duration and robustness of targeted immune responses by requiring active uptake of antigens by antigen presenting cells at the injection site. DPX-Survivac incorporating survivin targets within the DPX platform is therefore a relevant approach for treatment of survivin-expressing cancers to generate strong T cell responses that infiltrate tumors and result in measurable anti-tumor responses. Methods: 121 patients with platinum sensitive or resistant, advanced ovarian, fallopian tube or peritoneal cancer were treated with DPX-Survivac with or without drug combinations. Data from 3 different clinical trials...
e17550Background: DPX-Survivac is a novel T cell activating therapy containing a mix of HLA class... more e17550Background: DPX-Survivac is a novel T cell activating therapy containing a mix of HLA class I peptides designed to evoke a T cell response against survivin, optimized for cytotoxic activity w...
e14578Background: Survivin is strongly expressed in tumors of about 60% of diffuse large B-cell l... more e14578Background: Survivin is strongly expressed in tumors of about 60% of diffuse large B-cell lymphoma (DLBCL) patients. DPX-Survivac contains survivin HLA class I peptides in a novel formulation...
5576 Background: DPX-Survivac is a novel T cell activating therapy designed to elicit an effectiv... more 5576 Background: DPX-Survivac is a novel T cell activating therapy designed to elicit an effective immune response against recurrent ovarian cancers that express the survivin protein. The survivin specific T cells induced by DPX-Survivac can infiltrate the tumors and are associated with clinical responses. It is likely that achieving an anti-tumor effect requires a favorable ratio of T cells to tumor cells. Epacadostat (E) is an IDO1 enzyme inhibitor that may enhance effector T cell proliferation, shifting the tumor microenvironment (TME) away from an immunosuppressive state toward one supporting productive immune response. Methods: Recurrent ovarian cancer patients with advanced and metastatic progressive disease were treated with DPX-Survivac, intermittent low dose CPA with or without E. In the Phase 1b, 53 subjects were enrolled to receive DPX-Survivac, low dose CPA and E BID. In the Phase 2, 12 subjects were randomized to receive DPX-Survivac and low dose CPA with or without E. ...
Neoantigens are emerging targets for personalized cancer vaccines that provide patient specific c... more Neoantigens are emerging targets for personalized cancer vaccines that provide patient specific cancer immunotherapies. Many algorithms have been developed to select the most immunogenic neoantigens to include, however not all neoantigens chosen will generate equivalent immune responses, nor may they induce effective anti-tumour activity. To maximize immunological activity, selected peptides should be delivered simultaneously in a formulation that can stimulate potent, sustained immune responses to many different peptides. The DepoVaxTM platform is an oil-based system that uses lipids to incorporate many different types of antigens and adjuvants into a single formulation. Using a set of neoantigens identified from murine B16-F10 melanoma, we optimized a DepoVax formulation method that allows us to incorporate up to 14 neoantigens with a polynucleotide based adjuvant in a single formulation. These selected neoantigens irrespective of their solubility and hydrophobicity were formulated in DepoVax with the contents completely soluble in oil. C57BL/6 mice were vaccinated with 14 synthetic long peptide neoantigens (each 27 amino acids in length) prepared in DepoVax or in an aqueous formulation containing poly ICLC adjuvant. The immune responses were assessed eight days later by IFN-γ ELISPOT using splenocytes. Several of the peptides generated strong immune responses that were significantly higher in mice vaccinated with the DepoVax formulation compared to the aqueous formulation. To assess the contribution of CD8+ and CD4+ T cell responses, splenocytes from vaccinated mice were stimulated with an immunogenic peptide and intracellular IFN-γ/TNF-α producing CD8+ or CD4+ T cells were detected by flow cytometry. The highest production of TNF-α was detected by CD8+ T cells. Biological activity of the vaccines was assessed after one month storage at -20, 5 and 25 °C by IFN-γ ELISPOT assay; no significant difference was detected compared to the initial results. Analytical characterization of 14 peptides in DepoVax carried out using high-performance liquid chromatography (RP-HPLC), detected no significant chemical modifications or degradation of peptides after storage at -20 °C for up to 3 months compared to the initial results. These results demonstrate that the DepoVax platform can incorporate at least 14 neoantigens in a single formulation. Neoantigens formulated in DepoVax are stable for at least 3 months and our manufacturing method can incorporate peptides with a wide range of physical and chemical characteristics. This formulation generates strong CD8+ T cell responses, in excess of those induced by an aqueous formulation. The DepoVax platform is a promising solution to inducing robust immune responses to multiple neoantigens in a single formulation. Citation Format: Valarmathy Kaliaperumal, Genevieve Weir, Rajkannan Rajagopalan, Arthvan Sharma, Heather Torrey, Alecia MacKay, Ava Vila-Leahey, Cynthia Tram, Andrea Penwell, Leeladhar Sammatur, Marianne Stanford. A novel delivery platform containing up to 14 neoantigens can induce robust immune responses in a single formulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1726.
3072 Background: Survivin is important in apoptosis, proliferation, and angiogenesis. High expres... more 3072 Background: Survivin is important in apoptosis, proliferation, and angiogenesis. High expression has been linked to progression and drug resistance. DPX-Survivac vaccine (DPX) contains a mix of survivin HLA class I peptides designed to evoke a cytotoxic T cell response against survivin. This trial reports the safety and immune response profiles of DPX in combination with metronomic low dose oral cyclophosphamide (CPA) in ovarian cancer (OC). Methods: 40 Stage IIc-IV OC patients with no evidence of disease progression post-platinum chemotherapy were enrolled. Adverse events and dose limiting toxicities (DLT) were defined by CTCAE v4.03. Immune correlates (MDSCs; T regs; B cells) and vaccine induced T cell immunity (ELISpot; tetramer analysis) was assessed in purified PBMC and blood. Clinical response was assessed by CT and CA125. Results: 34/40 pts had an HLA match with the vaccine. Local injection site reactions (ISR) were the main DLT with 2 grade 3 skin ulcerations in cohort C. One hematological gr...
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