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CAR T therapy testing—how it started and how it’s going

Published Date

CAR T Therapy Testing

Introduction

Utilizing the body’s immune system to combat diseases such as cancer has energized the field of cellular therapy research and immuno-oncology. With the success of chimeric antigen receptor-modified T cells (CAR Ts) against hematologic malignancies, this therapy has demonstrated tremendous promise as well as unveiled hurdles that require further testing to unlock its full potential.

CAR Ts have been traditionally thought of as a method to accomplishing personalized medicine and have been mostly tested on disseminated tumors. The application of CAR Ts in solid tumors remains a work in progress for a myriad of reasons. For starters, solid tumors present some unique challenges, including the targetable antigens expressed on cancer cells are often expressed on healthy cells and the inability of T cells to infiltrate the solid tumor microenvironment (for review, see Leon et al., 2020). At The Jackson Laboratory (JAX), we are working with our customers to test CAR T efficacy in solid tumors and evaluate new approaches to CAR T technology, including combinations studies such as CAR Ts and checkpoint inhibitors. JAX leverages its strength to run cutting-edge studies and test the efficacy of preclinical treatments in vivo.
 

First, some basics...

The CAR T services offered from JAX utilize the NSG™ platform to deliver a modular system for CAR T therapy development and is a fast way to evaluate therapeutic efficacy by tumor growth inhibition measured by flow cytometry or in vivo imaging systems. We have worked with many partners to test efficacy in a disseminated tumor model.  Furthermore, the NSG™ MHC Class I/II DKO model, which  combines the features of the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency, MHC class I molecule (H2-K and D) deficiency, and MHC class II molecule deficiency (IA), provides delayed Graft-versus-Host Disease (GvHD) onset, which can help you confidently assess body weight loss due to CAR T toxicity or tumor burden – and not GvHD. You can also potentially extend the CAR T study length.
 

And where it’s going…

While the traditional method of generating CAR Ts and having an in vivo platform for efficacy testing is crucial, working with customers to go beyond the “traditional methods” of even nascent technologies is at the crux of JAX’s innovative platforms.

We are partnering with researchers globally to investigate many novel applications and development procedures, including:

  • CAR T efficacy testing in solid tumors derived from cell lines or Pateient Derived Xenografts
  • CD34 humanized autologous models of CAR T through ex vivo transduction and injection into CD34 humanized mice as a model of B cell aplasia
  • Co-transplantation of CAR T and donor PBMCs for a short-term model of B cell aplasia
  • In vivo transduction of T cells to generate CAR Ts in CD34 humanized mice
  • Allogeneic “of the shelf” CAR T

Here are some examples of potential various CAR T studies

CAR T in a solid Tumor Model

CAR T in a Disseminated Tumor MOdel

CAR T in an autologous B Cell Aplasia Model

In VIVO Transduction of T Cells in a CD34+ Humanized Mouse Autologous B Cell Aplasia Model

Co Transplantation of CAR T and Donor PBMCS for a short-term model of B Cell Aplasia in B Cell Targeting CAR Ts

Summary

CAR T therapies have traditionally been developed for as a personalized medicine approach to certain cancers. JAX CAR T services provide an in vivo model to test the efficacy of a potential CAR T therapy, definitively showing that the effects are due to CAR T and not GvHD.

JAX is not only a place to outsource your studies but also a provider with experience taking on challenging new projects using new cutting-edge approaches to develop novel treatments.

Do you have a CAR T therapy candidate ready for preclinical testing? JAX has the experience to run your study. Visit our CAR T efficacy study page to learn more about these novel approaches from JAX.

Recommended Resources

https://resources.jax.org/jax-blog/advancing-humanized-nsg-sup-tm-sup-mice-for-immuno-oncology-efficacy-testing

https://resources.jax.org/immuno-oncology-oncology/car-t-cell-therapy-are-we-there-yet

https://resources.jax.org/immuno-oncology-oncology/fda-approved-car-t-therapy-evaluated-in-nsg-mice

https://resources.jax.org/immuno-oncology-oncology/taking-car-t-therapy-for-a-preclinical-test-drive

https://resources.jax.org/immuno-oncology-oncology/the-abc-s-of-car-t-cell-therapies

 

References

Leon E, Ranganathan R, Savoldo B. (2020). Adoptive T cell therapy: Boosting the immune system to fight cancer. Sem Immunology. 49:

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