HALEY WOOLARD 

Canine Clinical Trials: Not Just a Walk in the Park

Many cancers remain refractory to conventional treatments,  

leading to considerable morbidity and mortality.  

Immunotherapeutic paradigms hold the promise of  

eliminating tumor cells in seemingly normal adjacent tissue  

and after metastatic spread. CAR T cells are among the most  

powerful of such therapies, engineering T cells to express  

chimeric receptors that can recognize tumor antigen without  

normal MHC restrictions. However, conventional production  

of CAR T cells is very labor intensive and expensive. Most  

preclinical studies of cancer therapy occur in rodent models,  

which although useful, have serious limitations including the genetic homogeneity of the animals,  the artificial nature of the neoplasms, which are created through injecting cell lines into young  and otherwise healthy animals, the artificial nature of the animals’ environment and the small size  of the tumors produced. As a result, many promising therapies showing success in these models  fail when moved into human clinical trials. Dogs develop cancer at rates very similar to humans  and the spontaneous tumors that they develop recapitulate most human cancers. Moreover,  utilizing pet dogs as models for human cancers obviates most concerns associated with rodent  models. We propose here to leverage our expertise in novel CAR-T cell creation using alginate  scaffolds to generate canine CAR T cells in an expedited and cost-effective manner. Scaffold 

generated canine CAR T cells will be analyzed for activation and stem cell phenotypes,  proliferative ability, cytokine production and in vitro killing of canine cancer cell lines.

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Market research was conducted to examine various cancers that remained refractory to conventional treatments, resulting in significant morbidity and mortality. Immunotherapeutic paradigms were seen as holding promise in the elimination of tumor cells in seemingly normal adjacent tissue, even after metastatic spread. Among these, CAR T cells emerged as one of the most potent therapies, involving the engineering of T cells to express chimeric receptors capable of recognizing tumor antigens without normal MHC restrictions. However, the conventional production of CAR T cells was known to be labor-intensive and expensive.

In the past, most preclinical studies of cancer therapy occurred in rodent models. While these models were useful, they had inherent limitations. The genetic homogeneity of the animals, the artificial nature of the neoplasms induced by injecting cell lines into young and otherwise healthy animals, the environment’s artificiality, and the small size of the tumors produced were noted drawbacks. Consequently, many therapies that showed promise in these models failed when transitioning into human clinical trials.

It was understood that dogs develop cancer at rates quite similar to humans, and the spontaneous tumors they develop mimic most human cancers. This realization highlighted the potential of utilizing pet dogs as models for human cancers, circumventing many concerns associated with rodent models.

The proposal aimed to leverage expertise in novel CAR-T cell creation using alginate scaffolds to expedite and cost-effectively generate canine CAR T cells. The plan involved analyzing scaffold-generated canine CAR T cells for activation and stem cell phenotypes, proliferative ability, cytokine production, and in vitro killing of canine cancer cell lines. The successful completion of this project was expected to provide a robust platform to facilitate canine trials, offering better insights for potential treatments to move into human clinical trials. This approach sought to de-risk some of the significant efforts and expenses typically associated with bringing human therapeutics to the market.