T-Cell Therapy for Glioblastoma: Personalized Immunotherapy
Featuring: Wayne Carter, DVM, PhD
In short
Wayne Carter, DVM, PhD, of TVAX Biomedical explains a personalized T-cell immunotherapy being studied for glioblastoma — one that uses a patient's own tumor cells and immune cells rather than a one-size-fits-all engineered drug. The approach involves vaccinating the patient with their inactivated tumor cells, collecting and expanding the resulting T cells, and infusing them back within seven days. Early human trial data showed 20% of patients living five years or longer, with a median survival of 17 months.
- •TVAX Immunotherapy is currently enrolling newly diagnosed, MGMT-negative glioblastoma patients who have not yet had chemotherapy or radiation and can provide a cubic centimeter of fresh tumor tissue — ask your care team if you qualify.
- •Timing matters: immunotherapy tends to work better when your immune system is still strong, so if possible, discuss it with your doctor before starting chemotherapy, radiation, or steroids.
- •The 'vein to vein' turnaround for TVAX is seven days — much faster than personalized neoantigen vaccines (months) or CAR-T therapy (three to five weeks).
- •Because this therapy uses your own T cells, it avoids the immune rejection side effects seen with some engineered therapies — a point worth discussing with your oncologist when comparing treatment options.
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“This is a personalized therapy.
Meeting Summary
Patients with difficult-to-treat cancers, such as glioblastoma, see immunotherapies as offering one of the best paths to a durable response. An immunotherapy fights the cancer system with the immune system, and the side effects can be more appealing than the side effects of other treatments, like chemotherapy, which weakens the immune system.
One immunotherapy is a personalized cancer vaccine, which is attractive because it offers a possible treatment option to nearly every cancer patient. Personalized cancer vaccines can be used to introduce or stimulate selected T cells (a kind of white blood cell, part of the immune system) to attack cancer cells.
A personalized cancer vaccine leverages the immune system's ability to see self/normal versus non-self/foreign cells and attack the non-self/foreign cells through a tailored antitumor response to their tumor mutation signature.
The vaccine is trying to get your body to produce enough of the right T cells, and then combine it with other personalized drug combinations to make sure that those T cells can do their job and win the battle against the tumor.
Another immunotherapy technology that is similar is “tumor infiltrating lymphocytes” (TIL), where they take your tumor sample, find the T cells that are in that sample, verify that those T cells are the ones that are supposed to be there doing the job, then expand those and inject them back into the patient. Wayne Carter, DVM, PhD, President and CEO, TVAX Biomedical, is uniquely qualified to discuss the cutting edge of immunotherapy technologies.
TVAX Immunotherapy® uses your T cells to fight your cancer. The key distinction of the TVAX Immunotherapy® is that it uses both a cancer vaccine pre-treatment to generate cancer-specific T cells and an activated “killer” T cell treatment. This proprietary immunotherapy approach has demonstrated efficacy against numerous cancers with low toxicity. TVAX Biomedical received Fast Track Designation from the FDA for TVAX Immunotherapy®.
Their first application of the technology is in glioblastoma multiforme (GBM). Dr. Carter has more than 18 years of Fortune 500 experience in pharmaceutical 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. D. in Immunology from Purdue University.
How does your immune system fight cancer? 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?
•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.
•Cancer neoantigen : a new protein that forms on cancer cells when certain mutations occur in tumor DNA
•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. 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?
•Apply the therapy to other cancer types once glioblastoma approval is achieved
•Combine the T cell therapy with other approaches like checkpoint inhibitors or Optune
•Combine with an oncolytic virus
•Add in more doses of T cells
•Educate patients, caregivers, and physicians that the more we can maintain the integrity of the immune system, the better patients are going to be able to fight their cancer 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. Meeting Notes KEYWORDS t cells, patients, question, antigens, vaccine, tumor, cancer, vaccination, immune system, cells, therapy, study, immunotherapy, surgery, response, technology, treatment, gbm, cancer cells, recurrent SPEAKERS Wayne Carter (69%), Brad Power (13%), Chris Apfel (7%), Gitte Pedersen (3%), Richard Anders (2%), Roger Royse (2%), Robb Owen (2%), Allen Morris (2%), Mark Stoner (1%), Brian McCloskey (1%) ADDITIONAL CHAT PARTICIPANTS Bill Paseman, Ryan Moon, Martin Luzbetak, Vanessa Hugo SUMMARY Wayne Carter discussed TVAX, a startup with an innovative approach to a personalized immunotherapy for cancer, specifically glioblastoma. The technology involves isolating and attenuating tumor cells, vaccinating patients with these cells, and then infusing activated T cells. The 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. OUTLINE Introductions: Wayne Carter and TVAX Overview
•Wayne Carter is based in Athens, Georgia, and his company is headquartered in Kansas City.
•The focus initially is on glioblastoma, and in the future a wider applicability of the technology.
•The technology uses T cells, which bind to cancer cells.
•The therapy is personalized, not engineered, and has the potential to treat any cancer due to its personalized nature.
•The technology is a polyclonal cancer neoantigen-specific adoptive T cell therapy.
•They have fast track designation by the FDA for newly diagnosed glioblastoma. Technology and Clinical Benefits
•The process: a surgeon removes a tumor, cells are isolated, attenuated with radiation, combined with GM-CSF, and vaccinated into the patient.
•The immune system responds.
•T cells are primed against the cancer.
•A study on dogs with bone cancer showed significant survival benefits with immunotherapy.
•The USDA Center for Veterinary Biologics approved the treatment of bone cancer in dogs. Human Clinical Study and Current Study Design
•A study on recurrent high-grade glioma showed improved survival with the therapy.
•Treating patients with a healthy immune system and minimal residual disease is best.
•The current study design focuses on newly diagnosed MGMT-negative patients with minimal residual disease, with inclusion criteria, timeline, and the control group receiving adjuvant temozolomide. Q&A Session: Timeline and IL-2
•Brad Power asks about the timeline and adjuvant therapy choices, and Wayne explains the design based on expert consultation.
•Brad Power inquires about the use of IL-2, and Wayne explains its role in continuing T cell expansion in vivo.
•Robb Owen asks about treatment options for his friend with glioblastoma, and Wayne explains the emergency authorization process.
•Gitte Pedersen asks about the selection of new antigens, and Wayne explains the polyclonal approach and the use of whole cell suspensions. Q&A Session: Cost, Adverse Events, and Clinical Trial Design
•Richard Anders asks about the cost of the therapy, and Wayne explains the competitive pricing compared to existing CAR T therapies.
•Richard Anders inquires about autoimmune manifestations, and Wayne explains the lack of such issues due to the use of the patient's own T cells.
•Richard Anders asks about the clinical trial design, and Wayne explains the decision to go with a one-to-one randomized trial.
•Brad Power answers a question about the duration of the therapy, and Wayne explains the seven-day vein-to-vein time and the potential for expansion. Q&A Session: Immune Response and Combination Therapies
•Roger Royce asks about the immune response, and Wayne explains the use of delayed- type hypersensitivity (DTH) response.
•Brian McCloskey asks about pre or post immune profiling, and Wayne explains the focus on getting an approval first.
•Vanessa Hugo asks about the therapy's potential, and Wayne explains the limitations due to the pre-surgery trial enrollment requirement.
•Wayne discusses the potential combination with Optune and checkpoint inhibitors. Q&A Session: Technical Questions and Recruitment Challenges
•Chris Apfel asks about the vaccination process and the number of cells injected, and Wayne explains the use of anti-CD3 and the rationale behind the vaccination schedule.
•Chris Apfel inquires about the possibility of getting the therapy outside the study, and Wayne explains the emergency authorization process.
•Chris Apfel asks about the recruitment challenges, and Wayne explains the issues with fresh tissue and the need for more sites and neurosurgeons.
•Chris Apfel asks about the long-term survival benefits, and Wayne explains the importance of maintaining the immune system's integrity. Q&A Session: Additional Questions and Future Directions
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