“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer”

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] Brad Power and Kristen Warren October 30, 2024 “Blocking TNF with existing, approved FDA drugs may enhance immunotherapy efficacy in prostate cancer by reprogramming the tumor microenvironment to promote a more robust anti- tumor immune response.

” – Ida Deichaite, PhD Meeting Summary Advanced prostate cancer patients are always searching for more treatment options, especially since each therapy eventually fails. Immunotherapies for cancer are very attractive since they can result in a more durable response, and the side effects can be less severe.

Prostate cancer has been considered a harder cancer type to apply immunotherapies to, yet research continues on new approaches. One of these is using a particular protein, the Tumor Necrosis Factor, to control the immune response. The translational goal is to make prostate cancer respond to immunotherapies.

Ida Deichaite, PhD, Assistant Adjunct Professor, Radiation Medicine and Applied Science, at the University of California, San Diego, is uniquely qualified to describe the state of research into therapies using the Tumor Necrosis Factor to modulate the immune response in prostate cancer. Dr. Dechaite's background is in virology and molecular biology.

She is conducting genomics analysis to identify susceptibility targets for aggressive cancers. The overarching goal of her research program is to identify and validate actionable targets and new targetable mechanisms for oncology diagnostic and therapeutic development.

Her bench-to-bedside approach to studying real-world genomics paired with clinical data facilitates rapid translation into the clinic and access to patients. What should you know about this novel immunotherapy approach? This is a hypothesis, like many, of a possible avenue for controlling cancer, in this case focused on prostate cancer.

The hypothesis is that blocking a particular protein (Tumor Necrosis Factor) with existing drugs approved by the FDA that may enhance immunotherapy efficacy in prostate cancer by reprogramming the tumor microenvironment to promote a more robust anti-tumor immune response.

It is in a research phase and will have to go through clinical trials, which are being developed, before it will be accessible to patients. The opportunity is to launch an exploratory clinical study to test the hypothesis of using TNF inhibitors in combination with checkpoint inhibitors.

The study would involve pre-treating patients with TNF inhibitors and analyzing biomarkers of immunosuppression post-treatment. How can you learn more about this? ●Contact Ida Deichaite at ideichaite@health.ucsd.edu.

“How a Particular Protein (Tumor Necrosis

t this? ●Contact Ida Deichaite at ideichaite@health.ucsd.edu. The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] Meeting Notes KEYWORDS TNF inhibitors, prostate cancer, immune response, checkpoint inhibitors, tumor microenvironment, inflammatory response, E-selectin, IL-6, RNA sequencing, clinical trial, immunosuppression, biomarkers, patient data, translational approaches, immunotherapy efficacy.

SPEAKERS Ida Deichaite (70%), Brian McCloskey (14%), Robb Owen (7%), Brad Power (6%), Rick Davis (2%), Saed Sayad (0%), Alane Watkins (0%) CHAT CONTRIBUTORS Robb Owen, Rick Davis, Alane Watkins, David Plunkett, Stephen Barry, Alexander Lalov, Ryan Moon, Chris Apfel SUMMARY Dr.

Ida Deichaite from UC San Diego presented her research on tumor necrosis factor (TNF) and its role in prostate cancer immune response. She hypothesized that blocking TNF with FDA-approved drugs could enhance immunotherapy efficacy by reprogramming the tumor microenvironment.

Her study, involving 49 and 169 prostate cancer patients, showed TNF expression increased with disease progression, while IL-6 and E-selectin levels decreased. The data suggested TNF's immunosuppressive role in prostate cancer. She proposed a clinical trial combining TNF inhibitors with checkpoint inhibitors to test this hypothesis.

The discussion also explored potential complementary research with CAR-T cell therapy and the use of TNF inhibitors in combination with androgen ablation blockers. OUTLINE Introductions ●Dr. Ida Deichaite of UC San Diego has contributed to the field of radiation medicine and applied science.

●She focused here on “translational” approaches and patient groups, aiming to bridge the gap between research and applications that are accessible to patients. ●Her hypothesis is that blocking the tumor necrosis factor (TNF) with FDA-approved drugs may enhance immunotherapy efficacy in prostate cancer.

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] ●Dr. Deichaite explains TNF's multiple roles in inflammatory processes, including initiating and regulating the body's response. ●TNF's involvement in activati

rostate cancer. Overview of TNF's Role in Inflammation and Immunology

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] ●Dr. Deichaite explains TNF's multiple roles in inflammatory processes, including initiating and regulating the body's response.

●TNF's involvement in activating endothelial cells and increasing vascular permeability to help immune cells reach affected tissues is discussed. ●The dual function of TNF in inflammation and immunosuppression is highlighted, with a focus on its potential role in prostate cancer. ●She mentions the widespread use of TNF inhibitors in autoimmune diseases and their established safety profile.

Genomic Study and Bioinformatics Analysis ●Dr. Deichaite describes the bioinformatics study of prostate cancer genomics, focusing on RNA sequencing data from patients at the Moores Cancer Center (UCSD). ●The study aimed to understand the inflammatory microenvironment in prostate cancer, comparing localized and metastatic disease.

●TNF expression was consistently observed in prostate cancer, with an increase in expression as disease progresses. ●IL-6 expression was found to regress in metastatic disease, contrary to expectations, leading to further investigation. Correlation with Checkpoint Inhibitors and Immune Cells ●Dr.

Deichaite discusses the correlation between TNF expression and checkpoint inhibitors, using data from a study by Caris involving thousands of patients. ●The study showed a statistically significant effect of TNF expression on checkpoint inhibitor expression, suggesting that the cold tumor microenvironment may not be due to a lack of checkpoint inhibitors.

●The analysis of immune cell subgroups showed an increase in M2 macrophages (a critical part of the tumor microenvironment, regulating a wide range of processes, including cancer cell progression) in later stages of prostate cancer. ●The big opportunity is blocking TNF to enhance checkpoint inhibitor efficacy by reprogramming the tumor microenvironment.

E-Selectin and TNF Expression in Prostate Cancer ●Dr. Deichaite explains the role of E-selectin in endothelial cells and its activation by TNF, highlighting its importance in the tumor vasculature. ●The study found a significant reduction in E-selectin protein expression in tumor tissues compared to normal tissues and BPH.

●Correlation with overall survival data showed that high E-selectin expression was associated with significantly better outcomes. ●The dual high expression of E-selectin and low TNF expression was found to be a significant predictor of overall survival in prostate cancer patients.

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] ●The opportunity is to launch an exploratory clinical study to test the hypothesis of using

ogy

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] ●Dr. Deichaite explains TNF's multiple roles in inflammatory processes, including initiating and regulating the body's response.

●TNF's involvement in activating endothelial cells and increasing vascular permeability to help immune cells reach affected tissues is discussed. ●The dual function of TNF in inflammation and immunosuppression is highlighted, with a focus on its potential role in prostate cancer. ●She mentions the widespread use of TNF inhibitors in autoimmune diseases and their established safety profile.

Genomic Study and Bioinformatics Analysis ●Dr. Deichaite describes the bioinformatics study of prostate cancer genomics, focusing on RNA sequencing data from patients at the Moores Cancer Center (UCSD). ●The study aimed to understand the inflammatory microenvironment in prostate cancer, comparing localized and metastatic disease.

●TNF expression was consistently observed in prostate cancer, with an increase in expression as disease progresses. ●IL-6 expression was found to regress in metastatic disease, contrary to expectations, leading to further investigation. Correlation with Checkpoint Inhibitors and Immune Cells ●Dr.

Deichaite discusses the correlation between TNF expression and checkpoint inhibitors, using data from a study by Caris involving thousands of patients. ●The study showed a statistically significant effect of TNF expression on checkpoint inhibitor expression, suggesting that the cold tumor microenvironment may not be due to a lack of checkpoint inhibitors.

●The analysis of immune cell subgroups showed an increase in M2 macrophages (a critical part of the tumor microenvironment, regulating a wide range of processes, including cancer cell progression) in later stages of prostate cancer. ●The big opportunity is blocking TNF to enhance checkpoint inhibitor efficacy by reprogramming the tumor microenvironment.

E-Selectin and TNF Expression in Prostate Cancer ●Dr. Deichaite explains the role of E-selectin in endothelial cells and its activation by TNF, highlighting its importance in the tumor vasculature. ●The study found a significant reduction in E-selectin protein expression in tumor tissues compared to normal tissues and BPH.

●Correlation with overall survival data showed that high E-selectin expression was associated with significantly better outcomes. ●The dual high expression of E-selectin and low TNF expression was found to be a significant predictor of overall survival in prostate cancer patients.

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] ●The opportunity is to launch an exploratory clinical study to test the hypothesis of using TNF inhibitors in combination with checkpoint inhibitors. ●The study would involve pre-treat

rotein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] ●The opportunity is to launch an exploratory clinical study to test the hypothesis of using TNF inhibitors in combination with checkpoint inhibitors. ●The study would involve pre-treating patients with TNF inhibitors and analyzing biomarkers of immunosuppression post-treatment.

●Robb Owen shares his experience with using TNF inhibitors and other treatments to manage cancer, emphasizing the importance of neurotransmitters and diet in cancer treatment. ●Brad Power raises questions about the broader implications of TNF inhibitors on various immunotherapies and the potential for modulating the immune response. Discussion on TNF and Immunotherapy ●Dr.

Deichaite explains the lack of studies showing that blocking TNF affects the efficacy of checkpoint inhibitors, suggesting it may be a promising approach. ●The discussion touches on the complexity of modulating the immune response and the potential for TNF inhibitors to enhance immunotherapy efficacy.

●Brad Power asks about the intersection of Ida's research with other immunotherapy approaches, such as CAR-T and neoantigen vaccines. ●Dr. Deichaite and Brian McCloskey discussed the complementary nature of their research and the potential for combining TNF inhibitors with other immunotherapies. Questions and Answers ●Dr.

Deichaite answered questions about the stage of prostate cancer patients suitable for TNF treatment and the potential for combining TNF inhibitors with androgen ablation blockers. ●The discussion included the importance of diagnostics and tests to personalize treatment and the potential for collaboration with BostonGene for larger data sets.

●She emphasized the need for further research to validate the findings and explore the potential of TNF inhibitors in clinical trials.

“How a Particular Protein (Tumor Necrosis Factor) Might Control the Immune Response in Prostate Cancer” (Ida Deichaite, PhD) [#118] TRANSCRIPT Brian McCloskey: We are very happy to have Dr. Ida Deichaite from UC San Diego join us. Ida is an assistant Adjunct Professor of radiation medicine and applied science at UC San Diego.

She's a molecular biologist by training, and she's been doing significant research on tumor necrosis factor, TNF, and its relationship to immune response in prostate cancer. Beyond that, she is the director of industry relations at Moores Cancer Center.

Ida and I go back to, I think 2017, when she boldly asked me to present some hair brain idea that I had about how medicine should be approached, and we've been fast friends ever since then. She and her teams have been very helpful in terms of looking at my genomic and multiomic data to identify potential treatment options. She’s an amazing friend, and we are looking forward to having her talk.

This is not medical advice, it is information you may take to your medical team. Always consult your physician.