This article is more than 5 years old. Information may no longer be current.
Roswell Park Comprehensive Cancer Center launches novel adoptive T-cell therapy trial
A clinical trial underway at Roswell Park Comprehensive Cancer Center is designed to assess the safety and efficacy of a two-pronged strategy that arms the immune system to more effectively attack cancer cells.
Patients treated for various cancer types through this early-stage clinical trial will receive one-time injections of their super T cells, which will be reprogrammed to more effectively target tumor cells.
“It is an approach that allows the immune system to be on the offense and defense at the same time,” Richard Koya, MD, PhD, associate director of the Roswell Park Center for Immunotherapy, said in a press release. “We arm the T cells with a receptor to help them ‘hunt down’ the cancer cells along with a TGF-beta blocker gene to suppress the suppressor. The result of this double gene modification — forcing expression of the T-cell receptor to target NY-ESO-1, and adding a blocker gene to nullify the effect of TGF-beta — is a super T cell engineered to both more effectively target cancer cells and resist the tumor’s attack.”
HemOnc Today spoke with Koya about the trial, how this strategy compares with other T-cell therapies, and why he is optimistic this may be an effective approach to cancer treatment.
Question: What prompted this research?
Answer: This trial is a combination of many years of research in our lab, especially in terms of testing new types of cancer treatments with T cells. We have been working with T-cell therapies and trying to engineer T cells by utilizing gene therapy and introducing certain genes into the T cells to make them recognize the tumor with tumor antigens. Working in the lab and testing preclinical tumor models, we have found that, when utilizing a protein T-cell receptor (TCR) against the NY-ESO-1 target, this target is only expressed in tumor cells and not in adult normal healthy cells. We additionally introduced another element, known as dominant-negative transforming growth factor (TGF)-beta receptor II. TGF beta is a protein that is secreted by the tumor in high amounts and suppresses the immune system. Introducing this gene blocks the effect of TGF beta in T cells only and acts as a shield protecting T cells against the suppressive effect of TGF beta. So, in a way, we are making a super T cell that can go to the tumor site and target the NY-ESO-1 antigen. This is the basic research that we have been working on over the years and attracted the NIH, which awarded us with a grant to conduct this current work.
Q: How will the study be conducted?
A: The clinical trial has launched and our first patient was enrolled in August. We will accrue roughly 24 patients with various types of advanced-stage solid tumor cancers, including ovarian cancer, melanoma and sarcoma. The phase 1 part of the trial will examine the safety and feasibility of our new approach. The phase 2 trial will assess the efficacy of the treatment.
Q: How exactly does this two-pronged strategy work?
A: We first gather blood from patients. The blood is then processed at our facility, and we gather the T cells and add a viral vector to induce expression of the TCR and dominant-negative TGF beta receptor. We then expand the cells for some time — approximately 2 days — and then we inject those T cells back into the patient. The entire process takes about 1 week, which is unique in our trial design. We have two Good Manufacturing Practice facilities at Roswell Park Comprehensive Cancer Center supporting this work, which can only be done in a few places in United States.
Q: How does this compare to other T-cell therapies — such as chimeric antigen receptor (CAR) T-cell therapy — in terms of approach, cost and effectiveness?
A: There are two CAR T-cell platforms that are approved and are already standard of care, targeting leukemia and lymphoma tumors. However, for solid tumors, this therapy seems to be less efficacious. Although CAR T cells are derived from an antibody, the TCR approach on which our dnTGF-beta therapy is based is different in that it recognizes the major histocompatibility complex molecules on the surface of cells, so it does not share CAR T cells’ limitations. We, along with many other scientists in the field, believe that the CAR T-cell therapy will have very limited application for solid tumors and the TCR approach is the way to go with solid tumors. Moreover, we are combining the TCR approach with a T-cell receptor and an element that blocks TGF-beta’s effect on T-cells. This strategy is unique to our institution.
Q: Why are you optimistic that this may be a good therapeutic approach?
A: As a field, we have hit enormous challenges treating patients with metastatic disease. There are other treatment approaches that are appealing, but they are not 100% efficient. Our two-pronged approach essentially provides patients with cancer with a new immune system. We do not need to rely on the patient’s own immune system, which is often suppressed. We are very optimistic about this approach based on the results of our extensive preclinical data in breast cancer, ovarian cancer, melanoma and bladder cancer, among other malignancies. We hope our unique approach will provide benefit, and we look forward to seeing the outcome of our clinical trial.
Q: What is the timeline for when the trial will be complete and data will be available?
A: We predict that we will finish our accrual within 1 year and we will need to then analyze the data. The clinical data itself should be mature within 1 or 2 years, maximum.
Q: Is there anything else that you would like to mentio n ?
A: We believe our unique platform differs from any others out there. The study is open to adults with various types of advanced cancer whose tumors express NY-ESO-1. Anyone who wants more information or who wants to enroll patients on the study can call (877) 275-7724 or send email to askrpci@roswellpark.org. – by Jennifer Southall
For more information:
Richard Koya, MD, PhD, can be reached at Roswell Park Cancer Institute, Elm and Carlton streets, Buffalo, NY 14263; email: richard.koya@roswellpark.org.
Disclosure: This work is funded by grants from NCI and Roswell Park Alliance Foundation. Koya is co-founder of Tactiva Therapeutics, an immuno-oncology spinoff from Roswell Park Comprehensive Cancer Center.