Cell Therapy: Looking to the Future of CAR T

Pursuing a multitude of diverse approaches in cell therapy to attack disease from new perspectives

November 11, 2020

Piecing Together the Cell Therapy Puzzle

Cell therapy has the potential to revolutionize the way scientists approach addressing blood cancers. Since the integration of Bristol Myers Squibb and Celgene – and with it, Juno, a pioneer in the development of chimeric antigen receptor (CAR) T and T cell receptor (TCR) T cell therapeutics – cell therapy research has been a core pillar of Bristol Myers Squibb’s cancer research efforts. 

The company has a diverse pipeline advancing early- and late-stage CAR T therapies in blood cancers, including multiple myeloma, lymphoma and leukemia. Autologous CAR T cell therapies seek to modify the patient’s own T cells to recognize and bind to proteins found on the surface of cancer cells, with limited expression on normal cells.

While there have been some notable successes in the cell therapy space, especially in blood cancers, fulfilling the promise of cell therapy requires continued innovation. Bristol Myers Squibb is investing in the future of cell therapy in myriad ways, including engineering next-generation approaches that leverage translational insights and tackle the numerous challenges of solid tumors. In addition, Bristol Myers Squibb is investing in improved manufacturing platforms and “off-the-shelf” approaches – to advance the science as quickly as possible for patients. 

“Our cell therapy program represents just one of many areas of cancer research at Bristol Myers Squibb – and in cell therapy alone we’re relentlessly pursuing multiple early approaches, in collaboration with several leading research partners,” said Kristen Hege, senior vice president, Early Clinical Development, Oncology/Hematology and Cell Therapy. “We think there is significant future opportunity, which is why we’re leaving no stone unturned. By looking at all these different areas in cell therapy, we’re poised to move quickly on the approaches that the science shows will provide the greatest benefit for patients.”

As one example, Bristol Myers Squibb is advancing its proprietary NEX-T manufacturing platform, which is being designed to reduce turnaround time and costs while increasing product quality and control. Additionally, with its strategic partners, Bristol Myers Squibb is advancing early, cutting-edge research approaches in cell therapy that include: 

  • Engineered TCR modified T cells for solid tumors, which can recognize tumor-specific proteins normally found on the inside of cells, whereas CAR T cells recognize proteins expressed on the surface;
  • Dual antigen targeting CAR T approaches that can help mitigate antigen loss and may result in more efficacious therapies. There are two distinct approaches: 
    • Two CARs may be expressed from a single vector, resulting in one engineered T cell with two receptor types (e.g., “bicistronic” or “dual CAR”); and
    • Two separate vectors may be used, each expressing one CAR, resulting in two separate populations of engineered T cells comprising one therapy (e.g., “carpool”).
  • CAR T cells armed with tunable, or custom payloads aimed to overcome tumor microenvironment resistance; and
  • Allogeneic or “off-the-shelf” CAR T cells made from T cells of healthy donors rather than the patient’s own reprogrammed T cells and can be delivered to patients without manufacturing wait time.

Rapidly Pursuing Cell Therapy Scientific Innovation for Patients

 

Bristol Myers Squibb’s cell therapy research team is uniquely equipped to gain insight into next-generation strategies in cell therapy. With 1,300 patients treated across six indications and 11 manufacturing process variations, Bristol Myers Squibb scientists have access to a remarkable depth of CAR T product, translational and clinical data, one of the largest datasets in the industry. 

“Cell therapy as a field can move quickly from first-in-human to registration studies, so it’s particularly crucial to be able to analyze data quickly and parse out new, impactful insights,” said Teri Foy, senior vice president, Research and Early Development Immuno-Oncology (I-O) and Cell Therapy. “Through machine learning and other sophisticated approaches, we’re using data to deliver critical insights that inform and optimize patient selection, process improvements, as well as engineering and combination approaches to address resistance mechanisms – and these insights are all the more valuable given that our datasets are derived from multiple indications and manufacturing processes.” 

Scientists are also applying learnings from I-O resistance in solid tumors and overcoming hostile tumor microenvironments to better guide next-generation strategies in cell therapy.

With multiple cell-based therapeutic approaches under investigation in blood cancers and beyond, Bristol Myers Squibb’s researchers are focused on harnessing the immune system to reimagine the future of cell therapy and ultimately bring potentially life-changing cell therapies to more patients as quickly as possible.

Did You Know? 

Like many of the most important scientific innovations, cell therapy has a surprising history. In 1996, the first U.S. clinical trials evaluating CAR T were in HIV infected, discordant twin pairs and later in patients with metastatic colorectal cancer. 

In 2012, researchers found CAR T therapy showed promise in cancer treatment when a six-year-old girl with acute lymphoblastic leukemia received an experimental treatment that used a disabled form of the HIV virus to genetically modify the immune cells and enable them to kill cancer. The successful treatment helped to launch the explosion of CAR T development. Learn more about the history of cell therapy and other advances in cancer research here.