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Grants to fund study of immunotherapy, virotherapy for three cancer types
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The Alliance for Cancer Gene Therapy awarded $1.3 million worth of grants to fund three clinical trials that will evaluate immunotherapy and virotherapy for glioblastoma, sarcoma and ovarian cancer.
The Alliance for Cancer Gene Therapy (ACGT) — established in 2001 — is the nation’s only nonprofit organization dedicated exclusively to cell and gene therapy treatments and immunotherapy for all cancer types. The alliance has provided young investigator and clinical translational grants for 16 years and has given more than $26 million directly to scientists.
Recipients of the 2017 ACGT clinical investigator grants are Nori Kasahara, MD, PhD, co-leader of the viral oncology program at Sylvester Comprehensive Cancer Center at University of Miami; Seth Pollack, MD, assistant member of the clinical research division at Fred Hutchinson Cancer Research Center; and Daniel Powell Jr., PhD, director of immunotherapy for the division of gynecology, and associate professor of pathology and laboratory medicine at University of Pennsylvania Perelman School of Medicine.
“ACGT’s clinical investigator grants allow these scientists to advance their research from the laboratory to the bedside for patients in clinical trials, providing an opportunity to see these treatments work in actual patients and hopefully save lives,” John Walter, CEO and president of ACGT, said in a press release. “Our goal at ACGT is to truly make an impact on how cancer is treated through the use of gene and cell therapies so that one day, cancer will be a treatable and manageable disease.”
HemOnc Today spoke with Margaret Cianci, executive director of ACGT, about why the alliance selected these three projects for grant funding, how each trial will be conducted, what these studies are designed to investigate and the projected timelines for each trial.
Q: Why did ACGT select these three projects for grant funding?
A: We chose these three projects for a number of reasons. We believe they are transformative, they have a very good chance of getting through the entire approval and trial process, and they are innovative in treating solid tumors and sarcomas.
Q: How will each project be conducted and what are they designed to investigate?
A: Two of the three projects are true clinical translational grants — the work by Kasahara and Pollack. They have already developed and tested the treatments with animal models, but now they need to test the safety and efficacy using biopsy samples to ensure that the treatments they are suggesting will in fact allow them to apply for an IND from the FDA and start a human trial. Kasahara’s research will focus on virotherapy for glioblastoma. Using a modified retrovirus to deliver chemotherapy directly into cancer cells, these ‘suicide genes’ continue to replicate to prevent recurrence. The work will take the experience in the lab and translate it to a patient clinical trial. Pollack’s work will focus on using immunotherapy to target sarcoma, a rare form of cancer that grows in connective tissue — cells that support other body tissue in bones, muscles, tendons and more. The initial clinical trial will deploy two different types of genetically engineered T cells to target the cancer and to assess efficacy and safety. For the third grant, Powell will enroll nine patients with ovarian cancer into a new clinical trial. Immune system killer T cells will be developed outside the body and reinserted to establish an offense against the disease and a defense against recurrence. So much of the work that was done with CAR T-cell therapy at University of Pennsylvania, which we helped fund, is now allowing scientists like Powell to use that knowledge to target solid tumors, specifically ovarian cancer. He will be enrolling patients this year.
Q: What are the potential timelines for each project?
A: The timelines for the three projects as outlined will be 2 to 3 years. Each of these grants award the recipients between $300,000 and $500,000.
Q: What is the potential promise of immunotherapy and virotherapy for each of these three malignancies?
A: In the case of Kasahara, he is a pioneer and true leading scientist of virotherapy. He has done a lot of work already in this area and what he is trying to do now is target malignant brain tumors. After surgery, chemotherapy and radiation, there are these cancer stem cells that remain in the brain. The question becomes, how do we target them and allow for continued targeting. Kasahara is using these modified viruses to infect the cancer cells and then deliver what we call suicide genes to trigger a compound that will then keep replicating and continue to kill the cancer cells, all while leaving normal healthy cells alone. He expects to combine this with immune checkpoint inhibition and to be able to treat malignant and metastatic brain tumors.
Pollack is taking a lot of the work that has been done in the CAR T-cell immunotherapy space and is now combining two types of CAR T cells for a first in-human, first-in-class trial designed to test for the synergies between specific T cells that are newly engineered with new receptors.
Powell is using the CAR T-cell therapeutic platform to treat ovarian cancer. Applying this form of immunotherapy to solid tumors has been a huge opportunity, but also a huge challenge. He is developing new clinical strategies for ovarian cancer by using CAR T cells specifically for certain novel targets common in ovarian tumors.
Q: What other projects are underway or in the planning stages?
A: In addition to the three clinical investigators that we funding [with these grants], we are also funding two young investigators. Greg Delgoffe, MD, professor at University of Pittsburgh, is using T-cell therapy to treat melanoma. T cells require an enormous amount of fuel to perform their tumor-killing functions. In solid tumors, cancer cells evade immune responses in part by depriving the T cell of the ability to generate energy. Delgoffe will use genetic engineering to reprogram tumor specific T cells, making them more fit to fight cancer for an extended period. The second grant we are funding is for Marco Gallo, MD, of University of Calgary. He is working on glioblastoma, and he is trying to target the cancer stem cells that look like weeds after they have removed the tumor. He is looking into how we can therapeutically get rid of those cancer cells by using a protein that will alter the DNA architecture of the cancer stem cells.
Q: Is there anything else that you would like to mention for our readers?
A: One of the things that makes this all possible is public funding. We are always looking for support to fund more research. We do leave a lot of good research on the table because we do not have enough funding. Moving forward, we will be focusing strategically on the idea of systemic treatments, treating metastatic cancers and better understanding the tumor microenvironment.
Our process for grant approval is quite intense. We invite investigators from all over the United States and Canada to submit letters of intent. Our scientific council reviews the letters of intent, and about 30% to 40% are invited to submit full applications. Two peer reviewers then review those applications on an NIH scale and, based upon the scores, we submit the applications to our scientific advisory council and they decide whom to recommend to our board of directors. To date, we have funded more than $28 million in grants. – by Jennifer Southall
For more information:
Margaret Cianci can be reached at Alliance for Cancer Gene Therapy, 96 Cummings Point Road, Stamford, CT 06902.
Disclosure: Cianci reports no relevant financial disclosures.