Researchers load CAR T cells with oncolytic virus to treat solid cancer
tumors

Date:
April 13, 2022
Source:
Mayo Clinic
Summary:
Researchers 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.



FULL STORY ========================================================================== 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 combination approach, published inScience Translational
Medicine,involves loading CAR-T cells, which are engineered to look for antigens on cancer cells, with an oncolytic virus. Oncolytic viruses
are naturally occurring viruses that can infect and break down cancer
cells. They either naturally replicate well in cancer cells or can be engineered to selectively target cancer cells.

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. "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." The therapeutic strategy addresses two major challenges that
make solid tumors difficult to treat with CAR-T cell therapy alone. First,
the oncolytic virus can break down the molecular shield that some solid
tumors use to avoid an immune system attack. Second, the virus can invade
into the core of the cancer cells -- a near-impossible feat for immune
cells alone, which often lose their power in the attempt.

The researchers also found that the combination approach provided an
immune memory phenotype against the tumor.



==========================================================================
"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." Using mouse models, Dr. Vile
and his team delivered the dual therapy intravenously to treat pediatric
and adult high-grade glioma, as well as melanoma in the skin. 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.

Next, Dr. Vile emphasizes it will be important to be cautious about how
well studies in animal models of cancer will translate into patient care.

"Nonetheless, we are hopeful that we will be able to take this strategy
into clinical trials within a year or two," Dr. Vile says. "By doing
such trials at Mayo Clinic, it will be possible to see if we can add
a further level of efficacy of CAR-T cell therapy to the treatment of
solid tumors of different types." Acknowledgments This work was funded
in part by Fraternal Order of Eagles Cancer Research Fund, Fellowship
Program, The European Research Council, The Richard M. Schulze Family Foundation, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Ventures, the NIH (R01CA175386, R01CA108961, P50 CA210964 to R.G. Vile),
a grant from Terry and Judith Paul, and a research grant from Oncolytics Biotech Inc. The salary of A. Huff and C. Driscoll was supported in part
by grant T32 AI132165 from the National Institutes of Health.


========================================================================== Story Source: Materials provided by Mayo_Clinic. Original written by
Susan Murphy. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Laura Evgin, Tim Kottke, Jason Tonne, Jill Thompson, Amanda L. Huff,
Jacob van Vloten, Madelyn Moore, Josefine Michael, Christopher
Driscoll, Jose Pulido, Eric Swanson, Richard Kennedy, Matt
Coffey, Houra Loghmani, Luis Sanchez-Perez, Gloria Olivier,
Kevin Harrington, Hardev Pandha, Alan Melcher, Rosa Maria
Diaz, Richard G. Vile. Oncolytic virus-mediated expansion of
dual-specific CAR T cells improves efficacy against solid tumors
in mice. Science Translational Medicine, 2022; 14 (640) DOI:
10.1126/scitranslmed.abn2231 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220413141538.htm

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