"Researchers at Mayo Clinic's Center for Individualized Medicine have devised an immunotherapy technique that combines chimeric antigen receptor-T cell therapy, or CAR-T cell therapy, with a cancer-killing virus to more effectively target and treat solid cancer tumors." "The study suggests CAR-T cells can deliver the oncolytic virus to the tumor. Then the virus can infiltrate tumor cells, replicate to bust the cells open, and stimulate a potent immune response. "This approach allows the tumor to be killed by the virus as well as by the CAR-T cells," explains Richard Vile, Ph.D., co-leader of the Gene and Virus Therapy Program within Mayo Clinic Cancer Center and the Richard M. Schulze Family Foundation Professor. "In addition, when the virus is delivered, it turns the tumor into a very inflammatory environment, which the patient's own immune system then sees and starts to attack."
"By putting the virus onto the CAR-T, we activate them against both the virus and the tumor, and they acquire immunological memory," Dr. Vile says. "This allows us to give a boost with the virus at a later time point, which in turn makes the CAR-T cells wake up again and undergo additional rounds of killing the tumor."
They found that the combination therapy led to high cure rates in tumors in multiple sites without causing significant toxicity. They also found it resulted in apparent protection in the cured mice against tumor recurrence.
"Clinically, delivering the therapy systemically is a potential advantage because you could possibly treat patients with metastatic disease without having to inject each tumor," Dr. Vile explains.
https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-researchers-load-car-t-cells-with-oncolytic-virus-to-treat-solid-cancer-tumors/#:~:text=The%20study%20suggests%20CAR%2DT,%22%20explains%20Richard%20Vile%2C%20Ph.
October 14, 2022 04:46 pm
"By putting the virus onto the CAR-T, we activate them against both the virus and the tumor, and they acquire immunological memory," Dr. Vile says. "This allows us to give a boost with the virus at a later time point, which in turn makes the CAR-T cells wake up again and undergo additional rounds of killing the tumor."
They found that the combination therapy led to high cure rates in tumors in multiple sites without causing significant toxicity. They also found it resulted in apparent protection against tumor recurrence.
September 17, 2022 11:34 am
The Mayo Clinic study is published in Science Translational Medicine, a prestigious peer reviewed journal, and was posted here beforehand with the release of ONCY's press release. The press release can be found on ONCY's website.
SAN DIEGO, Calif. and CALGARY, AB, April 14, 2022 /CNW/ -- Oncolytics Biotech® Inc. (NASDAQ: ONCY) (TSX: ONC) today announced the publication of preclinical data demonstrating the synergistic anti-cancer activity of pelareorep combined with chimeric antigen receptor (CAR) T cell therapy in solid tumors. The paper, entitled "Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice," was published in Science Translational Medicine in collaboration with researchers at several prestigious institutions, including the Mayo Clinic and Duke University. Preclinical studies published in the paper evaluated the persistence and efficacy of pelareorep-loaded CAR T cells ("CAR/Pela therapy") in multiple murine solid tumor models. The effects of combining CAR/Pela therapy with a subsequent intravenous dose of pelareorep ("pelareorep boost") were also investigated. Key data and conclusions from the paper include:
- The persistence and anti-cancer activity of CAR T cells improved drastically when loaded with pelareorep. Compared to either treatment alone, treatment with CAR/Pela therapy led to statistically significant survival benefits in murine skin and brain cancer models.
- CAR/Pela therapy followed by a pelareorep boost led to enhanced efficacy in murine skin and brain cancer models and tumor cures in >80% of treated mice in each model.
- Loading CAR T cells with pelareoep led to improved cancer cell targeting and prevented antigen escape in vivo by generating CAR T cells with dual specificity that target their designed antigen and the native T cell receptor antigen. These results indicate that CAR/Pela therapy may provide longer-lasting therapeutic benefits compared to treatment with CAR T cells alone.
https://www.oncolyticsbiotech.com/press-releases/detail/570/oncolytics-biotech-announces-publication-of-preclinical
In summary - the efficacy of pelareorep-loaded CAR T cells was augmented when the murine subjects received a subsequent intravenous dose (boost) of pelareorep, and overall demonstrated the ability of pelareorep-loaded CAR T cells to overcome the three most significant barriers to effective CAR T therapy by dramatically increasing CAR T cell persistence, reversing immunosuppressive TMEs, and reducing antigen escape.
September 17, 2022 02:32 pm
The demonstrated efficacy of ONCY's pelareorep to (1) dramatically increase CAR-T cell persistence, (2) reverse an immunosuppressive tumor microenvironment (TME) and (3) to overcome the attenuation of antigen escape induced by T-cell immunotherapy is showing to be a significant benefit of this pelareorep + CAR-T immuno-oncology (I/O) combination therapy, particularly after a subsequent intravenous boost of pelareorep is given following the initial dose of pelareorep + CAR-T therapy. September 18, 2022 06:40 pm
Barriers such as tumor heterogeneity and T cell exhaustion have exposed the weaknesses of various mono-immunotherapeutic approaches to GBM, including CAR T cell and checkpoint blockade strategies.
ONCY's pelareorep to (1) dramatically increase CAR-T cell persistence, (2) reverse an immunosuppressive tumor microenvironment (TME) and (3) to overcome the attenuation of antigen escape induced by T-cell immunotherapy is showing to be a significant benefit of this pelareorep + CAR-T immuno-oncology (I/O) combination therapy, particularly after a subsequent intravenous boost of pelareorep is given following the initial dose of pelareorep + CAR-T therapy.
Combining these three (3) complementary strategies, can proffer a rational means of mitigating these barriers and advancing therapeutic successes against GBM, pancreatic cancer and other solid tumors. September 19, 2022 07:54 pm
ONCY has demonstrated that the combination of pelareorep with CAR-T therapy and immune checkpoint inhibitors provides an effective measure to improve both CAR-T and immune checkpoint inhibitor function.
Combining the 3 complementary therapies could prove to be an effective means to increase CAR-T persistence and durability, reverse an immunosuppressive tumor microenvironment (TME), as well as gaining the ability to overcome both antigen escape and resistance induced by T-cell immunotherapy and checkpoint blockade, respectively.