Immunotherapy with genetically engineered T cells holds promise for the treatment of nonmalignant diseases in the dog

Nicola J. Mason Department of Pathobiology, Comparative Immunotherapy Program, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA

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 BVetMed, PhD, DACVIM

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Abstract

The ability to genetically redirect the antigenic specificity of T cells using chimeric antigen receptors (CAR) has led to unprecedented durable clinical remissions in human patients with relapsed/refractory hematological malignancies. This remarkable advance in successful immune cell engineering has now led to investigations into the application of CAR–T-cell technology to treat nonmalignant diseases. The use of CAR-T cells to target and eliminate specific cell subsets involved in the pathogenesis of autoimmunity, fibrosis, senescence, and infectious disease represents a new direction for adoptive cell therapies. While the use of CAR-T cells for nonmalignant disease is still in its infancy, early reports of dramatic clinical responses to CAR-T cells targeting CD19+ B cells in patients with severe autoimmune disease raise the possibility that this approach could lead to durable remissions, eliminating the need for ongoing conventional immunosuppressive therapies. Excitingly, nonmalignant disease processes that may be addressed by CAR–T-cell therapy in humans also occur in our canine populations. Given that technologies for developing canine CAR constructs are now available, robust protocols have been described for generating canine CAR-T cells, and experience is being gathered with their clinical use in oncology, it is anticipated that CAR-T cells will soon enter the veterinary clinics for the treatment of debilitating nonmalignant diseases. Here, we provide a broad overview of CAR–T-cell therapies for nonmalignant diseases and extrapolate these advances into the veterinary space, highlighting areas in which canine CAR-T cells are poised to enter the clinics for the treatment of nonmalignant disease.

Abstract

The ability to genetically redirect the antigenic specificity of T cells using chimeric antigen receptors (CAR) has led to unprecedented durable clinical remissions in human patients with relapsed/refractory hematological malignancies. This remarkable advance in successful immune cell engineering has now led to investigations into the application of CAR–T-cell technology to treat nonmalignant diseases. The use of CAR-T cells to target and eliminate specific cell subsets involved in the pathogenesis of autoimmunity, fibrosis, senescence, and infectious disease represents a new direction for adoptive cell therapies. While the use of CAR-T cells for nonmalignant disease is still in its infancy, early reports of dramatic clinical responses to CAR-T cells targeting CD19+ B cells in patients with severe autoimmune disease raise the possibility that this approach could lead to durable remissions, eliminating the need for ongoing conventional immunosuppressive therapies. Excitingly, nonmalignant disease processes that may be addressed by CAR–T-cell therapy in humans also occur in our canine populations. Given that technologies for developing canine CAR constructs are now available, robust protocols have been described for generating canine CAR-T cells, and experience is being gathered with their clinical use in oncology, it is anticipated that CAR-T cells will soon enter the veterinary clinics for the treatment of debilitating nonmalignant diseases. Here, we provide a broad overview of CAR–T-cell therapies for nonmalignant diseases and extrapolate these advances into the veterinary space, highlighting areas in which canine CAR-T cells are poised to enter the clinics for the treatment of nonmalignant disease.

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