From The Editor | April 10, 2024

2024: The Year of Development in Cell Therapy


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1


I look forward to receiving ARM’s Sector Snapshot in my inbox. Each edition is a one-stop report that shares detailed data and graphical information about a specific segment of the CGT space. The April 2024 edition focuses on the developments and advancements in engineered cell therapy in different international regions. ARM’s report offers an update on trends that drove cell therapy development in 2023 such as the increased effectiveness in treating blood cancer, accelerating progress in treating solid tumors, and clinical breakthroughs in treating autoimmune diseases. The report also provides an updated 2024 regulatory pipeline, predicting a new wave of approval for gene therapies to treat rare genetic diseases.

As of this article, three therapies have already been FDA-approved in the U.S. this year: Vertex and Crispr’s Casgevy, a gene editing therapy to treat sickle cell disease and beta-thalassemia; Iovance’s Lifileucel, a cell therapy to treat metastatic melanoma; and Orchard Therapeutics’ Libmeldy, a gene therapy to treat metachromatic leukodystrophy. We could see eight more regulatory decisions as well as five BLA or MAA submissions by the end of this year. Gene therapy led the league in approvals in 2023, but 2024 looks like cell therapy’s year. ARM states three trends are driving the developments: increased effectiveness in treating blood cancer; accelerating progress in treating solid tumors; and clinical breakthroughs in treating autoimmune diseases.

I have had many fruitful conversations with executives from industry and academia that speak directly to the three trends ARM highlights. Here are some examples of what CGT leaders have shared with me and with Cell & Gene’s readers about developments in cell therapy.

Increased Effectiveness in Treating Blood Cancer

As explained in Sector Snapshot, we will see increased effectiveness in treating blood cancers this year. The results for autologous CAR-T are extraordinary. Full stop. And the good news is that allogeneic therapies are progressing, too. The future for allogeneic therapies for blood cancers looks promising with ongoing research and development focused on enhancing the efficacy and safety of these treatments. Allogeneic therapies offer several advantages, including potentially stronger anti-cancer effects and the ability to induce graft-versus-tumor (GVT) effects, where the donor immune cells attack the cancer cells. Companies such as Orca Bio and Poseida Therapeutics are working on ways to reduce toxicities in allogeneic cell therapies to bring increased effectiveness to blood cancers.

Indeed, earlier this year, Poseida Therapeutics’ President and CEO, Kristin Yarema, Ph.D., wrote an article for Cell & Gene, Objectively Evaluating Innovative Therapies And Making Sense Of Emerging Data. In it, Yarema details why allogenic CAR-T compares favorably with autologous CAR-T, and why, in many ways, allo has advantages that auto cannot hope to match. And, as Poseida’s Mark Gergen wrote in his article for Cell & Gene, “Allo is not Auto with extra gene editing.  Allo should not be assumed to be inferior to Auto. That realization is starting to take hold.”

Allo is not without its challenges, however. One such challenge is Graft-versus-Host Disease (GvHD), a major complication of allogeneic transplantation where the donor cells attack the recipient's tissues. Research is focused on strategies to reduce the risk and severity of GvHD, including improved graft manipulation techniques and the use of pharmacological agents.

On a recent episode of Cell & Gene: The Podcast, Orca Bio’s CMO, Dr. Scott McClellan, joined me to discuss how and why toxicities continue to stymie allogeneic cell therapies. We talked about Orca Bio’s detailed plan to potentially lower the risk of GvHD. “Allo transplant, today, is often the only option people have for a cure,” says McClellan. “That cure is counterbalanced by a lot of risk. The risks are many, and one to highlight is Graft-versus-Host Disease. In many cases, the donor cells can recognize the recipient’s tissue as foreign and attack it just as would attack a pathogen.” He goes on to discuss acute GVHD and chronic GvHD, can be fatal, and even with it’s not fatal, there can be negative consequences for quality of life.

In Orca’s Phase Ib/II study, when measured against a concurrent, non-randomized single-center comparator for allogeneic transplant patients, Orca-T, the company’s investigational high-precision allogeneic cell therapy, is being evaluated in clinical trials for the treatment of multiple hematologic malignancies. McClellan shared that the study demonstrated preliminary evidence of significantly higher GvHD-free, relapse-free survival rates after 1 year; improved relapse-free survival rates; and lower rates of chronic GvHD.

Accelerating Progress in Treating Solid Tumors

On Episode 67 of Cell & Gene: The Podcast, Triumvira’s CEO, Dr. Paul Lammers, and I sat down to discuss the company's proprietary T cell Antigen Coupler, which has both autologous and allogeneic approaches. We talked through targeting relapsed or refractory HER2-positive solid tumors and CLDN18.2-positive solid tumors. Triumvira’s proprietary T cell Antigen Coupler (TAC) is a multi-domain chimeric molecule that works directly with the T cell receptor (TCR) to help a T cell recognize and attack cancer cells. Lammers and his team believe TAC will become an essential tool for safely and effectively treating patients with liquid and solid malignancies. The initial target of their TAC-based programs is Claudin 18.2, a surface cancer antigen frequently over-expressed in a broad range of solid tumors.

Another episode on solid tumors that’s worth a listen is Episode 28 of Cell & Gene: The Podcast featuring Dr. Carl June. It aired back in 2022, but Dr. June’s message is relevant today. Dr. June explained that due to the many current trials for various solid cancers, there are, in fact, “’glimmers of hope’ that there will be activity [with solid tumors],” he stated. “So far, we’ve been generally disappointed in solid tumors compared to the outstanding results in blood cancers. Research is showing the mechanisms of resistance in solid tumors. For instance, a pediatric brain cancer paper was published in Nature this year from a group at Stanford. In a small number of patients, in what is a uniformly lethal brain cancer in children where there’s literally almost no therapy once a diagnosis is made, they're now extending the lifespan of these children with CAR-T cell infusion. That’s promising, because it’s a solid tumor and it’s in the brain, which is traditionally difficult to treat with immunotherapy.”

Dr. June went on to report that there have been responses in prostate cancer, the most common cause of cancer in men. He noted that while more research is needed, he referenced a very exciting paper that was published recently in the New England Journal of Medicine about a group out of Portland, OR that used T-cells to treat a woman with metastatic pancreatic cancer, which had a “striking result.” And, so, “there are glimmers of hope that this issue in solid tumors will be solved now that many groups around the world are working on it,” he shared.

Clinical Breakthroughs in Treating Autoimmune Diseases

Recent clinical data provides cautious optimism for patients living with autoimmune diseases such as lupus, multiple sclerosis (MS), or rheumatoid arthritis (RA). The New England Journal of Medicine released an abstract, CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up, which states that of 15 patients — eight with lupus, four with systemic sclerosis (scleroderma), and three with idiopathic inflammatory myositis — researchers eliminated or reduced symptoms and disease biomarkers with a single infusion of CAR-T cells designed to target B cells. The abstract concludes, “In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials.”

For MS patients specifically, genome therapy is emerging as a breakthrough treatment option. However, genome therapy for MS is still mainly in the experimental and pre-clinical stages. Researchers are working to understand better the genetic and molecular mechanisms underlying MS and how they might be targeted through gene-based interventions. This article on Cell & Gene shares that in the context of MS, research is underway to target specific genes associated with the immune response and inflammation that characterize the condition. Genome therapy could target the underlying genetic factors contributing to the development or progression of the disease. Some potential approaches to genome therapy for MS include gene editing, gene delivery, stem cell therapy, immunomodulation, and more. The author stresses, “It's important to note that while the concept of using gene editing for MS is promising, several challenges need to be addressed. These challenges include the precision of gene editing, the delivery of the editing tools to the target cells in the central nervous system, potential off-target effects, and ethical considerations.”

There’s much more to come this year in cell therapy. To stay up to date on the latest developments, visit Cell & Gene regularly, watch your inbox for our e-newsletter, subscribe to Cell & Gene: The Podcast, and register for our Cell & Gene Live events.