“A Unique Personalized Killer T-cell Treatment for Glioblastoma

eutical and nutrition R&D. In his role at Pfizer as Executive Director of Global Clinical Development, he accelerated the development of many drugs using novel clinical technologies. His board appointments include MRI Global and Acenxion Biosystems. Dr. Carter received his B.S., D.V.M., and Ph.D. in Immunology from Purdue University. How does your immune system fight cancer?

“A Unique Personalized Killer T-cell Treatment for Glioblastoma" (Wayne Carter, DVM, PhD) [#110] The immune system has evolved to protect us from pathogens such as bacteria, viruses, and fungus. When an infection arises, the immune response is triggered, all of the infection is eliminated, and then the immune response goes back down.

But a memory of the infection persists, and you get a healthy memory cell, so that if you see that pathogen again, it can react quickly. But that doesn't happen in cancer, because if the tumor doesn't completely go away early in the process, the immune cells become exhausted, and are just not as functional.

So they may need to be reactivated, or even worse, the immune system never saw the tumor in the first place, because tumors can be clever, perhaps able to block recognition by the immune system. So there are a lot of hurdles: tumor evolution, tumor heterogeneity, different cells expressing different things and then this exhaustion phenomenon from the cells seeing the antigen too much.

How do immunotherapies work to treat cancer? Immunotherapies (a treatment leveraging your immune system) offer one of the best paths to a durable response -- they are fighting a biological system (your cancer) with another system (your immune system), rather than the hit-and-miss, less durable approach of targeting a biomarker with a single drug or poisoning your cancer with chemotherapy.

The idea is to try to find what's different about the tumor that is allowing it to avoid the immune system. Sometimes the tumor turns things back on that are generally turned off in people, sometimes it turns up the volume on things that are generally turned down. So if you can find these reactivated genes, you can perhaps get the immune system to recognize them and attack them.

But the immune system doesn't usually recognize them without a vaccine because a successful tumor shields itself from the immune system by being a terrible antigen-presenting cell.

Immunotherapies offer a treatment option to nearly every cancer patient because they are neither targeted to a specific “tissue of origin”, like lung cancer or colon cancer, nor are they targeted to a biomarker, a protein that your cancer cells overexpress, like BRCA or EGFR. What is the TVAX immunotherapy approach and how is it different from other immunotherapies?

overexpress, like BRCA or EGFR. What is the TVAX immunotherapy approach and how is it different from other immunotherapies? ●The TVAX approach isolates and inactivates the tumor cells, vaccinates patients with these cells, collects primed T cells from the patient via leukapheresis, activates and expands the T cells and then infuses activated effector T cells into the patient.

●The TVAX approach is different from other immunotherapies you may have heard of and considered, such as (1) immune checkpoint inhibitors (e.g., Keytruda/pembrolizumab, OPDIVO/nivolumab), (2) CAR-T (chimeric antigen receptor T-cell) therapy, or (3) personalized neoantigen vaccines.

It is closer to a (4) “TIL” therapy (Tumor Infiltrating Lymphocytes), which takes T cells found near your tumor, grows them in a lab, and infuses them into you. ●The TVAX technology is a “polyclonal cancer neoantigen-specific adoptive T cell therapy” – which is a mouthful of medical jargon.

Let’s break it down: ●Polyclonal: antibodies produced by multiple immune cells, or in this particular case multiple T cells derived from different tumor antigens.

“A Unique Personalized Killer T-cell Treatment for Glioblastoma" (Wayne Carter, DVM, PhD) [#110] ●Adoptive: taking your healthy cells, e.g.

, white blood cells, growing them in a lab, then putting them back into your blood ●T cell therapy: a type of immunotherapy that makes your immune cells better able to attack cancer ●A big advantage of expanding your own T cells and then infusing them back into you is that you don’t have problems with the side effects of rejection by your immune system which come from engineered therapies.

●The TVAX therapy has shown promising results in dogs with bone cancer, extending median survival from 4-10 months to 1900 days. In human trials, 20% of patients lived five years or longer, with a median survival of 17 months. The therapy is currently in a 120-patient study, focusing on newly diagnosed MGMT-negative patients. They are recruiting patients.

The therapy aims to be competitive in cost, potentially undercutting existing CAR-T therapies. ●The TVAX time from “vein to vein” – from collecting your T cells to expanding and reinfusing them – is seven days. For personalized neoantigen vaccines the design and manufacturing can take several months, and for CAR-T it is typically three to five weeks.

When should you consider getting immunotherapy? Many immunotherapies are still experimental. Most doctors will recommend that you should get the standard of care first and try something experimental later. The problem with that, for immunotherapy, is that you need your immune system to be able to respond.

If you get chemotherapy, radiotherapy, steroids, or other standard treatments, your immune system is beat up. If you can, it would be better to get immunotherapy first.

r. The problem with that, for immunotherapy, is that you need your immune system to be able to respond. If you get chemotherapy, radiotherapy, steroids, or other standard treatments, your immune system is beat up. If you can, it would be better to get immunotherapy first.

If you’ve had standard treatments, you should try to reset your immune system as best as you can to be able to get the most from a cancer vaccine or immunotherapy. As a tumor gets larger, it starts to get more heterogeneous and more diffused and spread out across multiple sites in the body. The microenvironment is more suppressive to the immune system.

Therefore the timing for trying immunotherapy is probably better when you have less cancer, or at an earlier stage. How can you access the TVAX immunotherapy? ●You can enroll in the current clinical trial if you have glioblastoma, are newly diagnosed (before surgery and have not been on other treatments), are MGMT negative, and have a cubic centimeter of fresh tissue.

●You can potentially access it on an emergency use basis. Ideally, you should not yet have had chemotherapy or radiation, so you have a strong immune system. ●You need a centimeter cubed of fresh tumor tissue. What’s next for TVAX and immunotherapy?

“A Unique Personalized Killer T-cell Treatment for Glioblastoma" (Wayne Carter, DVM, PhD) [#110] How can you learn more?

●For more on immunotherapies for cancer treatment, please see our discussions with: ○Lisa Butterfield on cancer vaccines here ○Willy Hoos on personalized neoantigen vaccines here ○Gary Onik on personalized in vivo immunotherapy for “cold” cancers here ○BostonGene on predicting immunotherapy response with a diagnostic test here ○Sumit Subudhi on immunotherapies in prostate cancer treatment here ○Matthew Dons on growing your white blood cells here ●For more on TVAX, please contact Wayne Carter at wcarter@tvaxbiomedical.

com. 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 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.

“A Unique Personalized Killer T-cell Treatment for Glioblastoma" (Wayne Carter, DVM, PhD) [#110] Meeting Notes KEYWORDS