This article is part of our 2024-25 Annual Report.
Melanoma has long been at the forefront of innovation in cancer treatment, paving the way for breakthroughs in immunotherapy and targeted therapies. However, despite remarkable progress achieved in recent years, challenges remain. For many patients, existing therapies are not enough. Next-generation cellular therapies—which focus on improving the patient’s own immune response against cancer—are now emerging as powerful tools to close this gap. These cutting-edge approaches offer new hope for patients with advanced or treatment-resistant melanoma, redefining what’s possible in the fight against this aggressive cancer.
Helping drive advancements in this field are Dr. Roda Amaria, Director of Clinical Research for the Melanoma Medical Oncology Group at MD Anderson Cancer Center, and Dr. Cristina Puig Saus, Assistant Professor in the Department of Microbiology, Immunology, and Molecular Genetics (MIMG) and the Department of Surgery - Division of Surgical Oncology at the University of California, Los Angeles (UCLA). The two researchers are leading the charge in cellular therapy development. Their work, alongside the MRA’s relentless support for new therapies, exemplifies the collective effort that is driving progress and saving lives.
“Our goal is to make TIL therapy even safer, smarter, and more effective for patients.”
- Dr. Roda Amaria
Few therapies embody the promise of next-generation cellular innovation more than tumor-infiltrating lymphocyte (TIL) therapy, which takes T-cells (white blood cells responsible for recognizing and destroying cancerous cells) directly from a patient’s tumor, amplifies their cancer-fighting potential in the lab, and reintroduces them to the body to attack the melanoma. Many cancer cell therapies are directed at a specific cancer target or targets. In contrast, autologous TIL cell therapy is designed to deploy billions of personalized, patient-specific TIL cells to recognize and attack cancer cells.
Dr. Roda Amaria is at the forefront of this field. “Our goal is to make TIL therapy safer, smarter, and more effective for patients,” Dr. Amaria explains. Recently, the FDA approval of Iovance Biotherapeutics’ lifileucel, a TIL therapy product branded as Amtagvi, marked a historic milestone. Based on a Phase II study showing that 31.4% of treated patients benefited significantly, Amtagvi now offers a viable treatment option for many patients who previously had no other therapeutic avenues.
The power of next-generation TIL therapy lies not just in its ability to improve patient outcomes but also in making these therapies more accessible and inclusive.
While this development is groundbreaking, Dr. Amaria sees room for improvement. “There are hurdles we need to overcome,” she says. Traditional TIL therapy requires surgery to harvest tumor samples, seven days of non-myeloablative chemotherapy to prepare the body, and a short course of interleukin-2 (IL-2), which has some challenges. New research, including work presented at the American Society of Clinical Oncology (ASCO) Annual Meeting by Obsidian Therapeutics and research on next-generation TIL therapy by Iovance, could reshape the landscape of TIL therapy. Employing genetic modifications, Dr. Amaria and her collaborators are exploring how TIL cells can be primed to function more effectively with fewer side effects. For example, Obsidian’s OBX-115 cells are equipped with an “on-off” switch activated by a simple pill. This allows clinicians to regulate treatment, delivering exceptional potency while mitigating toxicity. “It’s a potential game-changer for safety and efficacy,” says Dr. Amaria.
Iovance is also conducting a first-in-human trial at ten U.S. clinical trial sites of IOV-4001, a next generation TIL with PD-1 inactivation technology which has the potential to significantly improve the already impressive TIL clinical profile.
The power of next-generation TIL therapy lies not just in its ability to improve patient outcomes but also in making these therapies more accessible and inclusive. By incorporating advancements like genetic engineering and less invasive biopsy methods, researchers are working to bring hope to a broader pool of melanoma patients, even those with advanced age or coexisting conditions.
While TIL therapy builds upon naturally occurring immune responses, chimeric antigen receptor (CAR)-T therapy takes a different route. In this approach, custom-designed immune cells target melanoma with a precision akin to a laser-guided missile. It’s a truly personalized form of medicine, and at the forefront of this research is Dr. Cristina Puig Saus.
Dr. Puig Saus envisions CAR-T therapy as the future for patients whose tumors are resistant to other treatments. “Our CAR-T therapy is specifically tailored to melanoma biology,” she explains. By creating synthetic receptors that recognize proteins uniquely overexpressed by melanoma cells, her lab has developed a therapy that is finely tuned to destroy cancer without harming healthy tissues.
“Thanks to MRA, we’re able to connect with experts in different fields, fostering ideas we couldn’t achieve alone.”
- Dr. Cristina Puig Saus
One of the most exciting prospects of CAR-T therapy is its adaptability. Unlike conventional treatments that target one biological pathway, CAR-T therapy can evolve alongside emerging tumor challenges. For example, Dr. Puig Saus’ work also aims to expand CAR-T therapy to rare and aggressive melanoma subtypes, such as uveal, mucosal, and acral melanomas, which are often less responsive to traditional therapies.
However, translating CAR-T therapy to the clinic is far from simple. Dr. Puig Saus highlights funding as the greatest barrier to scaling this therapy. Despite securing FDA support for clinical trials, financial resources to move the therapy from research to treatment remain limited. “We have the science,” she says, “but without funding, it stops there.”
CAR-T therapy’s potential to transform melanoma care is immense, provided the necessary investment and collaboration are in place to carry it forward. MRA continues to fund research projects focused on developing and advancing therapies for patients with melanoma, including CAR-T.
Central to all this progress is MRA, which plays a pivotal role as both a funder and community builder. By investing time and support in groundbreaking projects, MRA helps accelerate therapies from the lab to the clinic. Their support ensures that innovative ideas — like genetically enhanced TIL or CAR-T cells — have the runway to mature into life-saving treatments.
MRA’s impact extends beyond research funding. One of its most essential contributions is building a collaborative ecosystem where researchers, clinicians, and advocates work together toward shared goals. “Collaboration is everything,” says Dr. Puig Saus. “Thanks to MRA, we’re able to connect with experts in different fields, fostering ideas we couldn’t achieve alone.”
Equally important to MRA is the patient voice. MRA’s annual Scientific Retreat and initiatives like the RARE Registry enable patients to share their stories and participate as stakeholders in the quest to improve melanoma outcomes. “It’s inspiring to see the passion of the melanoma community,” says Dr. Amaria.
The fight against melanoma demands relentless perseverance, scientific ingenuity, and united action. Researchers like Dr. Amaria and Dr. Puig Saus exemplify what’s possible when innovation and collaboration come together. From genetically enhanced TIL therapy offering life-saving possibilities to CAR-T therapy redefining personalized care, next-generation cellular therapies are reshaping the melanoma treatment landscape.
MRA’s unwavering support and the collective effort of the research and melanoma communities continue to push boundaries. While challenges remain, these innovative approaches promise a future where no patient faces the devastating impact of melanoma without options — or hope.
