Establishing a model system for evaluating CAR T cell therapy using dogs with spontaneous diffuse large B cell lymphoma

Panjwani, M. Kazim; Atherton, Matthew J.; MaloneyHuss, Martha A.; Haran, Kumudhini Preethi; Xiong, Ailian; Gupta, Minnal; Kulikovsaya, Irina; Lacey, Simon F.; Mason, Nicola J.

doi:10.1080/2162402x.2019.1676615

Cited by 38 publications

(45 citation statements)

References 42 publications

(48 reference statements)

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“…Furthermore, targeting CD20 + cells eventually resulted in antigen escape and the emergence of CD20 − disease. However, the study was able to show the successful lentivector production of functional canine CAR T cells, while also demonstrating that the challenges of effective CAR T cell therapy in animals were comparable to those seen in humans trials ( 134 ).…”

Section: Introductionmentioning

confidence: 84%

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

et al. 2020

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Treating individual patients on the basis of specific factors, such as biomarkers, molecular signatures, phenotypes, environment, and lifestyle is what differentiates the precision medicine initiative from standard treatment regimens. Although precision medicine can be applied to almost any branch of medicine, it is perhaps most easily applied to the field of oncology. Cancer is a heterogeneous disease, meaning that even though patients may be histologically diagnosed with the same cancer type, their tumors may have different molecular characteristics, genetic mutations or tumor microenvironments that can influence prognosis or treatment response. In this review, we describe what methods are currently available to clinicians that allow them to monitor key tumor microenvironmental parameters in a way that could be used to achieve precision medicine for cancer patients. We further describe exciting novel research involving the use of implantable medical devices for precision medicine, including those developed for mapping tumor microenvironment parameters (e.g., O 2 , pH, and cancer biomarkers), delivering local drug treatments, assessing treatment responses, and monitoring for recurrence and metastasis. Although these research studies have predominantly focused on and were tailored to humans, the results and concepts are equally applicable to veterinary patients. While veterinary clinical studies that have adopted a precision medicine approach are still in their infancy, there have been some exciting success stories. These have included the development of a receptor tyrosine kinase inhibitor for canine mast cell tumors and the production of a PCR assay to monitor the chemotherapeutic response of canine high-grade B-cell lymphomas. Although precision medicine is an exciting area of research, it currently has failed to gain significant translation into human and veterinary healthcare practices. In order to begin to address this issue, there is increasing awareness that cross-disciplinary approaches involving human and veterinary clinicians, engineers and chemists may be needed to help advance precision medicine toward its full integration into human and veterinary clinical practices.

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Section: Introductionmentioning

confidence: 84%

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

et al. 2020

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“…1‐8). Studies with CAR T cells and PD‐1/PD‐L1 blockade have been reported 9‐11 . When contrasted with tumor‐grafted murine models, spontaneous canine cancers exhibit genetic and epigenetic heterogeneity, complex tumor microenvironments, and immunoediting.…”

Section: Figurementioning

confidence: 99%

Dog leukocyte antigen‐88*034:01 presents nonamer peptides from canine distemper virus hemagglutinin, large polymerase, and matrix proteins

Nemec

Holmes

Hess

2021

HLA

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Canine spontaneous cancers may offer greater fidelity than rodent models in advancing clinical immunotherapies. Boxers in particular are distinguished as study subjects by their popularity, and high incidence of human‐relevant cancers. Further, the MHC class I allele DLA‐88*034:01, with a known motif, dominates the breed, facilitating discovery of shared CTL responses against mutation‐origin neoepitopes by standard prediction methods. We experimentally confirmed the allomorph's binding motif by developing an MHC surface stabilization assay. The assay validated four DLA‐88*034:01‐presented peptides from canine distemper virus, ubiquitously administered in routine vaccines, for positive controls in future CTL studies. In turn, these viral peptides substantiated motif‐based prediction for DLA‐88*034:01. The study adds new tools for studying neoepitope‐specific CTL in Boxers to foster canine 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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Establishing a model system for evaluating CAR T cell therapy using dogs with spontaneous diffuse large B cell lymphoma

Abstract: Mason (2020) Establishing a model system for evaluating CAR T cell therapy using dogs with spontaneous diffuse large B cell lymphoma, OncoImmunology, 9:1, 1676615,

Cited by 38 publications

References 42 publications

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

Dog leukocyte antigen‐88*034:01 presents nonamer peptides from canine distemper virus hemagglutinin, large polymerase, and matrix proteins

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

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