A Consortium Aims to Make CAR-T's Faster and More Affordable

Charles River is supporting the effort by developing an ex vivo platform that can expedite safety and efficacy tests

There is little doubt that chimeric antigen receptor (CAR)-T cells are a powerful weapon against cancer. The therapy, which works by turning a patient’s immune cells into heat-seeking missiles, with tumors as their target, has proven to be highly successful, and in some cases curative. There are now over a dozen CAR-T cell therapies approved worldwide, which primarily target B-cell malignancies and multiple myeloma.

By one estimate, more than 45,000 cancer patients worldwide have been treated with a CAR-T drug since the first ones reached the market. While that number might sound like a lot, it’s actually just a tiny fraction of the patients who might benefit from this novel approach. Due to their high cost and complex manufacturing, CAR-T drugs are among the most difficult drugs to develop and deliver, meaning that patients who need them often have difficulty accessing them.

The Easy Workflow Integration for Gene Therapy Consortium, or EASYGEN, is a European Union (EU)- backed effort trying to reduce some of these challenges by making CAR-T therapies more affordable and faster. In fact, their current goal is to develop a fully automated, hospital-based platform capable of manufacturing personalized cell therapies, including CAR-Ts,  within 24 hours. The aim is to optimize manufacturing and hospital workflows, thus reducing manufacturing time to under a day, cutting treatment costs by 50% and thus making CAR-Ts more accessible to more patients.

Charles River Laboratories is supporting the development of bedside CAR-T manufacturing by using its expertise in 3D screening technologies to develop an ex vivo platform to expedite early safety and efficacy screening of these life-changing drugs. 

“If you have a patient amenable to cell therapy, it can take a lot of time for them to access it,” says Julia Schueler, DVM, PhD, Therapeutic Area Lead, Oncology, Charles River. “Identifying the CAR-T candidates and then manufacturing them is a lengthy process, and the paperwork involved in developing these drugs can be a nightmare. The intent is to change that dynamic.”
Schueler’s lab at Charles River’s Freiburg site specializes in a highly personalized approach to oncology drug development that is part mouse and part human.

Cancerous tissue taken from human lungs, colons, breasts, and other organs is implanted in mice or murine cell lines. The models, known as patient-derived xenografts, are then used to identify which drugs might work for a specific patient or group of patients with similar profiles. They also study mechanisms of drug resistance and the tumor microenvironment, which provides the soil for tumors to seed and grow. 

The 3D screening platform they are developing as part of EASYGEN will ideally be able to identify and screen candidates that are most specific to a patient’s tumor, most effective, and, importantly, the least toxic in a matter of days. To accomplish this, the Freiburg team will be putting PDX tissue-derived cells into a 3D format and then use the PDX model as a surrogate for cancer patients. Schueler says PDX models are excellent tools for studying tumor heterogeneity, including different levels of target expression, because they maintain the genetic and phenotypic (functional) diversity of a patient’s original tumor. This makes them a good proxy for use in CAR-T drug development because those treatments are so precise and personalized.

“In the workflow, it is usually cancer type-agnostic, but we decided to focus initially on prostate cancer. There was an interest in this cancer type within the consortium. Additionally, prostate cancer is amenable to CAR-T treatment. If we get this up and running, we will then do the same screens for all tumor types.”

The EASYGEN Consortium is coordinated by the German healthcare company, Fresenius. In addition to Charles River, there are 13 other participants in this project from the academic and commercial sides. IDCQ HOSPITALES Y SANIDAD SL in Spain is a partner. 

Schueler says it has been rewarding to be part of this effort. “I always like partnering with other oncology groups, but I particularly like it if people are coming at the problem from different angles,” she said. “The GLP-perspective is totally different than things going on in my technical realm.”

For instance, she found it extremely interesting learning about the day-to-day work that radio clinics apply to patients receiving CAR-therapy. “For us, cell expansion tension is what we do day-to-day, but something an oncology nurse is not necessarily familiar with, so for projects like this, it is good to have people with totally different skills.”