Feasibility and safety of cCD20 RNA CAR-bearing T cell therapy for the treatment of canine B cell malignancies

Smith, Jenessa B.; Panjwani, M. Kazim; Schutsky, Keith; Gnanandarajah, Josephine S.; Calhoun, Sondra; Cooper, Laurence J.N.; Mason, Nicola J.; Powell, Daniel J.

doi:10.1186/2051-1426-3-s2-p123

Cited by 6 publications

(3 citation statements)

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“…Although a few studies have been reported on canine CAR-T cell therapy, [5][6][7][8][9] basic information of canine CAR-T cells is limited. Electroporated autologous T cells expressing first-generation CARs were administered to a dog with spontaneous B-cell lymphoma.…”

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confidence: 99%

Optimization of canine CD20 chimeric antigen receptor T cell manufacturing and in vitro cytotoxic activity against B‐cell lymphoma

Sakai

Igase

Mizuno

2020

Vet Comparative Oncology

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Canine B-cell lymphoma is one of the most common haematopoietic neoplasms in veterinary medicine, and it is considered a relevant model for human diffuse large Bcell lymphoma. Although the standard treatment consisting of multi-drug chemotherapy is effective in most cases, treatment is often challenging because of relapse and drug resistance. The adoptive transfer of autologous T cells genetically modified to express a CD19-specific chimeric antigen receptor (CD19 CART cells) has been shown to be highly effective in human B-cell malignancies. However, there is no clinically available canine CART cell therapy. We generated canine second-generation and third-generation CART cells by retroviral gene transduction. Optimization was performed to investigate effective viral transduction protocols and favourable culture conditions for canine CART cells. The RetroNectin-bound virus infection method resulted in more than 70% transduction efficiency. The effect of culture conditions on the phenotype of CART cells was evaluated by the expression of surface markers. in vitro cytotoxicity assays of target cells cultured with CD20 CAR-transduced cells demonstrated that CD20 CART cells exhibit cytotoxicity against CD20-expressing canine B-cell lymphoma cells and canine CD20-transduced murine cells, whereas no effect was observed against cells that lacked canine CD20 expression. Our study established virus-based canine CART cell generation, providing fundamental data for a better understanding of canine adoptive T-cell therapy.

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confidence: 99%

Optimization of canine CD20 chimeric antigen receptor T cell manufacturing and in vitro cytotoxic activity against B‐cell lymphoma

Sakai

Igase

Mizuno

2020

Vet Comparative Oncology

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“…Although several types of CAR-T cell therapies have already been approved in humans [104], there are still no approved CAR-T cell therapies for dogs. However, several groups, including our own, have already reported on how to create canine CAR-T cells with some efficacy in vitro [105] and in vivo [106][107][108]. To maximize the effect of CAR-T cell therapy in patients, CAR-T cells must be administered after myelosuppression using strong anticancer drugs and radiation to eliminate the immune cells.…”

Section: Next Generations Of Immunotherapy In Dogsmentioning

confidence: 99%

Spontaneously occurring canine cancer as a relevant animal model for developing novel treatments for human cancers

Mizuno

2021

Translational and Regulatory Sciences

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The most common cause of death among adult or older dogs is malignancy. Dogs spontaneously develop malignant tumors with age, and the incidence of malignant tumors in dogs is higher than that in humans. Basic research on treatment of tumors is generally conducted using syngeneic or immunodeficient mice, which have some shortcomings as a model for human tumors that develop over a long period of time, while interacting with the host immune system. On the other hand, naturally occurring canine tumors develop under immunocompetent conditions and may be suitable for preclinical studies, especially for the development of therapies that affect host immunity. In this review, some of the canine tumors and immunotherapies that have been implemented thus far will be discussed, with the intent of helping establish cancer treatment research, using dogs with naturally occurring tumors, for translational studies in humans.

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“…As with human medicine, these novel immunotherapies have been developed in veterinary medicine. In the literature, there are a few studies on canine CAR-T cell therapy [ 10 , 11 , 14 , 19 ]. For establishing the CAR-T cell therapy for canine lymphoma, we developed the strategy of preparing canine CD20-CAR-T cells in the previous report [ 16 ].…”

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Development of a monoclonal antibody for the detection of anti-canine CD20 chimeric antigen receptor expression on canine CD20 chimeric antigen receptor-transduced T cells

Sakai

Ogino

Tsukui

et al. 2021

The Journal of Veterinary Medical Science

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Chimeric antigen receptor (CAR) CAR-T cell therapy targeting CD20 can be a novel adoptive cell therapy for canine patients with B-cell malignancy. After injection of the CAR-T cells in vivo, monitoring circulating CAR-T cells is essential to prove in vivo persistence of CAR-T cells. In this study, we developed a novel monoclonal antibody against canine CD20 CAR, whose single-chain variable fragment was derived from the our previously reported anti-canine CD20 therapeutic antibody. Furthermore, we proved that this monoclonal antibody can detect therapeutic anti-canine CD20 chimeric antibody in the serum from healthy beagle dogs injected with the therapeutic antibody for safety study. This monoclonal antibody is a useful tool for monitoring both canine CD20-CAR-T cells and anti-canine CD20 therapeutic antibody for canine lymphoma.

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Feasibility and safety of cCD20 RNA CAR-bearing T cell therapy for the treatment of canine B cell malignancies

Cited by 6 publications

References 0 publications

Optimization of canine CD20 chimeric antigen receptor T cell manufacturing and in vitro cytotoxic activity against B‐cell lymphoma

Optimization of canine CD20 chimeric antigen receptor T cell manufacturing and in vitro cytotoxic activity against B‐cell lymphoma

Spontaneously occurring canine cancer as a relevant animal model for developing novel treatments for human cancers

Development of a monoclonal antibody for the detection of anti-canine CD20 chimeric antigen receptor expression on canine CD20 chimeric antigen receptor-transduced T cells

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