ORCID ID: https://orcid.org/0000-0002-2009-0416. Graduated from the Novosibirsk State University. Ph.D. from the Institute of Bioorganic Chemistry, Moscow. Worked at the Novosibirsk Institute of Molecular Biology, and biotechnological companies. Over 40 years of experience in genetic engineering, virology, immunology, and biotechnology. Manufactured drugs (Lydasum, Ingitrilum) and the anti-cancer drug candidates based on injectable (Reducin) and peroral (Aimpila) forms of AFP toxin(s) non-covalent complexes. Invented a supplement for stomach ulcer and IBD treatment. The author of a book, a book chapter, and many articles.
The immune system plays a pivotal role in combating diseases, including cancer, with monocytes em... more The immune system plays a pivotal role in combating diseases, including cancer, with monocytes emerging as key regulators of immune response dynamics. This article describes a novel strategy for cancer treatment centered on depleting myeloid-derived suppressor cells (MDSCs), to enhance the overall immune response while simultaneously targeting cancer cells directly. Alpha-fetoprotein (AFP) is an oncofetal protein that plays an important role in delivering nutrients to immature monocytes, embryonic, and cancer cells in a targeted manner. AFP can be repurposed, making it a vehicle for delivering toxins, rather than nutrients to kill cancer cells and deplete MDSCs in the tumor microenvironment (TME). Depleting monocytes not only stimulates the immune system but also improves the lymphocyte-to-monocyte ratio (LMR), often low in cancer patients. AFP combined with cytotoxic drugs, offers dual benefit—immune stimulation and targeted chemotherapy. Studies in xenograft models demonstrated high efficacy and safety of AFP-toxin conjugates, surpassing conventional targeted chemotherapy. Such conjugates have also been reported to provide superior efficacy and safety in cancer patients compared to chemotherapy. This approach, using AFP conjugated with toxins, either covalently or non-covalently, presents a safe and highly effective option for cancer immuno/chemotherapy.
3589 Background: Aimpila is a non-covalent complex of two natural compounds: porcine alpha-fetopr... more 3589 Background: Aimpila is a non-covalent complex of two natural compounds: porcine alpha-fetoprotein (PAFP) and a glycosidic apoptosis inducer (AI). PAFP is able to bind selectively to the AFP receptor-positive cancer cells and deliver the AI intracellularly due to AFP receptor-mediated endocytosis. The AI opens mitochondrial permeability transition pores, resulting in apoptosis. Preclinically, the complex is cytotoxic. We investigated the single agent activity of aimpila in patients (pts) with liver metastatic colorectal cancer (mCRC). Methods: Eligibility Criteria: Age >18 yrs, mCRC, any prior treatment, having documented progressive metastatic liver disease. Treatment consisted of oral capsules at a fixed sub-maximal dose (0.3 mg of active substance in an oral capsule, twice a day for 8 weeks). 12 pts were accrued, 6 chemonaïve; median ECOG performance status was 0, median age 56 years (range 45–65), and median time from previous treatment failure was 9.0 months (range 1–20). CT scans were performed before and after. Results: Of the 12 patients, 9 are evaluable for response by RECIST. Two achieved a complete response (CR), 1 a partial response (PR); subsequent confirmatory CT scans are pending. Three achieved stabilization (SD), in 2 cases = 2 months; 3 experienced disease progression. Of 3 non-evaluable pts, 1 experienced clinical deterioration without a CT scan, 1 experienced stable disease >2 months but with both lesions <10 mm in diameter, and a third developed nausea and vomiting leading to interruption of treatment, the only recorded significant adverse event. CEA estimations before and after treatment are available from 2 pts; 1 pt (radiological CR) going from 816 ng/ml to 268 ng/ml; the other (radiological SD) going from 1,243 ng/ml to 638 ng/ml. In this latter patient, one of the liver lesions disappeared, radiologically. The PR pt and 1 of the SD pts had progressed after previous oxaliplatin-based chemotherapy. Median survival has not yet been reached, with a median follow-up of 4 months. Conclusion: Single agent aimpila was well-tolerated in this patient population and produced major objective responses in some patients with liver mCRC. Further study is warranted. [Table: see text]
Cancer therapy & oncology international journal, Feb 18, 2022
Cancer is one of the leading causes of death globally. There are cancer treatments like chemother... more Cancer is one of the leading causes of death globally. There are cancer treatments like chemotherapy, radiotherapy, surgery, and immunotherapy. A combination of therapies can lead to a cancer cure. Myeloid-derived suppressor cells (MDSCs) activity prevents the success of many immune- and chemotherapies. MDSCs depletion prevails over other cancer immunotherapies because it activates both innate and adaptive immunity. On the other hand, the best-targeted chemotherapy specifically kills cancer cells, including cancer stem ones that are at the roots of metastases leading to 90% of deaths of cancer. The low differentiated MDSCs, cancer stem cells, and most cancers absorb alpha-fetoprotein (AFP) loaded with nutrients through AFP receptor (AFPR)-mediated endocytosis. So, the AFP-toxin drug is targeted chemotherapy that hits simultaneously to MDSCs and cancer cells. In my opinion, it is the perfect combination of the most powerful cancer immunotherapy and the best-targeted chemotherapy. For example, the AFP-maytansine conjugate demonstrated 100% survival in tumor-bearing T cell-deficient mice.
Journal of Stem Cell Research & Therapy, Nov 24, 2014
A good example of an effective anti-cancer strategy can be found in nature. Cytotoxic lymphocytes... more A good example of an effective anti-cancer strategy can be found in nature. Cytotoxic lymphocytes (CTL) can specifically recognize the “wrong” cell and then inject the granzyme B that activates caspases that cause inevitable apoptosis. Like CTL modern anti-cancer drugs should be specific and effective. Targeting drugs to cancer cells provides specificity while the drug intracellular target provides efficacy. Binding/de-binding of the specific and effective parts should be provided too. We tried to create an anti-cancer drug that includes all these features.
Oncofetal alpha-fetoprotein (AFP) activates in developing as well as in growing cancer cells. It ... more Oncofetal alpha-fetoprotein (AFP) activates in developing as well as in growing cancer cells. It delivers polyunsaturated fatty acids through specific cell receptors. AFP-binding receptors are also discovered on myeloidderived suppressor cells which suppress the immune response to the embryo and to the tumor. After AFP receptormediated endocytosis these cells release AFP for the next run for nutrients. The AFP natural shuttle delivery manner can be used for cancer treatments. Oncoshuttle is an exogenous AFP able to bind and deliver toxins instead of nutrients to cancer and myeloid-derived suppressor cells in a repeated way. Toxins for shuttling should have a higher than albumin or other blood proteins binding affinity to AFP. AFP wins the competition for the ligand over albumin due to its unique hydrophobic pocket. Injectable AFP-toxin non-covalent complexes, as well as oral porcine AFP-toxin ones, have demonstrated anticancer activity. The possible role of neonatal Fc receptor in t...
The “magic bullet” by Paul Ehrlich is a chemotherapeutic, which can precisely locate and destroy ... more The “magic bullet” by Paul Ehrlich is a chemotherapeutic, which can precisely locate and destroy tumor cells. For over 100 years, a great number of approaches have been developed for targeted delivery of toxins. Nevertheless, the progress in the battle with cancer is moderate. In reality, the magic bullet is unable to destroy cancer cells with 100% efficacy. However, cancer cells are neither an optimal nor the only possible target. The magic bullet needs a “magic target”.
The immune system plays a pivotal role in combating diseases, including cancer, with monocytes em... more The immune system plays a pivotal role in combating diseases, including cancer, with monocytes emerging as key regulators of immune response dynamics. This article describes a novel strategy for cancer treatment centered on depleting myeloid-derived suppressor cells (MDSCs), to enhance the overall immune response while simultaneously targeting cancer cells directly. Alpha-fetoprotein (AFP) is an oncofetal protein that plays an important role in delivering nutrients to immature monocytes, embryonic, and cancer cells in a targeted manner. AFP can be repurposed, making it a vehicle for delivering toxins, rather than nutrients to kill cancer cells and deplete MDSCs in the tumor microenvironment (TME). Depleting monocytes not only stimulates the immune system but also improves the lymphocyte-to-monocyte ratio (LMR), often low in cancer patients. AFP combined with cytotoxic drugs, offers dual benefit—immune stimulation and targeted chemotherapy. Studies in xenograft models demonstrated high efficacy and safety of AFP-toxin conjugates, surpassing conventional targeted chemotherapy. Such conjugates have also been reported to provide superior efficacy and safety in cancer patients compared to chemotherapy. This approach, using AFP conjugated with toxins, either covalently or non-covalently, presents a safe and highly effective option for cancer immuno/chemotherapy.
3589 Background: Aimpila is a non-covalent complex of two natural compounds: porcine alpha-fetopr... more 3589 Background: Aimpila is a non-covalent complex of two natural compounds: porcine alpha-fetoprotein (PAFP) and a glycosidic apoptosis inducer (AI). PAFP is able to bind selectively to the AFP receptor-positive cancer cells and deliver the AI intracellularly due to AFP receptor-mediated endocytosis. The AI opens mitochondrial permeability transition pores, resulting in apoptosis. Preclinically, the complex is cytotoxic. We investigated the single agent activity of aimpila in patients (pts) with liver metastatic colorectal cancer (mCRC). Methods: Eligibility Criteria: Age >18 yrs, mCRC, any prior treatment, having documented progressive metastatic liver disease. Treatment consisted of oral capsules at a fixed sub-maximal dose (0.3 mg of active substance in an oral capsule, twice a day for 8 weeks). 12 pts were accrued, 6 chemonaïve; median ECOG performance status was 0, median age 56 years (range 45–65), and median time from previous treatment failure was 9.0 months (range 1–20). CT scans were performed before and after. Results: Of the 12 patients, 9 are evaluable for response by RECIST. Two achieved a complete response (CR), 1 a partial response (PR); subsequent confirmatory CT scans are pending. Three achieved stabilization (SD), in 2 cases = 2 months; 3 experienced disease progression. Of 3 non-evaluable pts, 1 experienced clinical deterioration without a CT scan, 1 experienced stable disease >2 months but with both lesions <10 mm in diameter, and a third developed nausea and vomiting leading to interruption of treatment, the only recorded significant adverse event. CEA estimations before and after treatment are available from 2 pts; 1 pt (radiological CR) going from 816 ng/ml to 268 ng/ml; the other (radiological SD) going from 1,243 ng/ml to 638 ng/ml. In this latter patient, one of the liver lesions disappeared, radiologically. The PR pt and 1 of the SD pts had progressed after previous oxaliplatin-based chemotherapy. Median survival has not yet been reached, with a median follow-up of 4 months. Conclusion: Single agent aimpila was well-tolerated in this patient population and produced major objective responses in some patients with liver mCRC. Further study is warranted. [Table: see text]
Cancer therapy & oncology international journal, Feb 18, 2022
Cancer is one of the leading causes of death globally. There are cancer treatments like chemother... more Cancer is one of the leading causes of death globally. There are cancer treatments like chemotherapy, radiotherapy, surgery, and immunotherapy. A combination of therapies can lead to a cancer cure. Myeloid-derived suppressor cells (MDSCs) activity prevents the success of many immune- and chemotherapies. MDSCs depletion prevails over other cancer immunotherapies because it activates both innate and adaptive immunity. On the other hand, the best-targeted chemotherapy specifically kills cancer cells, including cancer stem ones that are at the roots of metastases leading to 90% of deaths of cancer. The low differentiated MDSCs, cancer stem cells, and most cancers absorb alpha-fetoprotein (AFP) loaded with nutrients through AFP receptor (AFPR)-mediated endocytosis. So, the AFP-toxin drug is targeted chemotherapy that hits simultaneously to MDSCs and cancer cells. In my opinion, it is the perfect combination of the most powerful cancer immunotherapy and the best-targeted chemotherapy. For example, the AFP-maytansine conjugate demonstrated 100% survival in tumor-bearing T cell-deficient mice.
Journal of Stem Cell Research & Therapy, Nov 24, 2014
A good example of an effective anti-cancer strategy can be found in nature. Cytotoxic lymphocytes... more A good example of an effective anti-cancer strategy can be found in nature. Cytotoxic lymphocytes (CTL) can specifically recognize the “wrong” cell and then inject the granzyme B that activates caspases that cause inevitable apoptosis. Like CTL modern anti-cancer drugs should be specific and effective. Targeting drugs to cancer cells provides specificity while the drug intracellular target provides efficacy. Binding/de-binding of the specific and effective parts should be provided too. We tried to create an anti-cancer drug that includes all these features.
Oncofetal alpha-fetoprotein (AFP) activates in developing as well as in growing cancer cells. It ... more Oncofetal alpha-fetoprotein (AFP) activates in developing as well as in growing cancer cells. It delivers polyunsaturated fatty acids through specific cell receptors. AFP-binding receptors are also discovered on myeloidderived suppressor cells which suppress the immune response to the embryo and to the tumor. After AFP receptormediated endocytosis these cells release AFP for the next run for nutrients. The AFP natural shuttle delivery manner can be used for cancer treatments. Oncoshuttle is an exogenous AFP able to bind and deliver toxins instead of nutrients to cancer and myeloid-derived suppressor cells in a repeated way. Toxins for shuttling should have a higher than albumin or other blood proteins binding affinity to AFP. AFP wins the competition for the ligand over albumin due to its unique hydrophobic pocket. Injectable AFP-toxin non-covalent complexes, as well as oral porcine AFP-toxin ones, have demonstrated anticancer activity. The possible role of neonatal Fc receptor in t...
The “magic bullet” by Paul Ehrlich is a chemotherapeutic, which can precisely locate and destroy ... more The “magic bullet” by Paul Ehrlich is a chemotherapeutic, which can precisely locate and destroy tumor cells. For over 100 years, a great number of approaches have been developed for targeted delivery of toxins. Nevertheless, the progress in the battle with cancer is moderate. In reality, the magic bullet is unable to destroy cancer cells with 100% efficacy. However, cancer cells are neither an optimal nor the only possible target. The magic bullet needs a “magic target”.
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