The Society for Immunotherapy of Cancer (SITC) 2024 meeting highlighted promising advances in cancer immunotherapy, particularly in the development of novel therapies for prostate and lung cancers. Researchers presented findings on T-cell engagers, new targets within the tumor microenvironment, and methods to enhance CAR T cell efficacy.
T-Cell Engagers Reshape Solid Tumor Treatment
New drugs utilizing T-cell therapy are changing the approach to attacking certain types of tumors. Of particular note is the recent FDA approval of a T-cell engager for small cell lung cancer. This approval is significant because it demonstrates the potential of T-cell therapies to be effective in solid tumors, a concept previously met with skepticism. According to Dr. Fong, this development "basically resets the whole field." Ongoing research focuses on developing T-cell engagers for prostate cancer, indicating a growing interest and investment in this therapeutic modality.
Targeting Myeloid Cells in Prostate Cancer
Research presented by Aram Lyu, PhD, from Dr. Fong's lab, focused on the tumor microenvironment of prostate cancer, identifying SPP+ macrophages as a key player in immunotherapy resistance. The study, published in Nature, found that these cells, which increase in number as prostate cancer progresses, express high levels of secreted phosphoprotein 1 (SPP1). Targeting these cells could potentially overcome immune suppression and slow tumor progression. Dr. Fong noted that these findings define a resistance mechanism used by "cold tumors" to evade immune responses, offering opportunities for patient selection and improved treatment strategies.
Enhancing CAR T Cell Efficacy with Mannose
Yapeng Su, PhD, presented research on enhancing CAR T cell efficacy through metabolic modulation. His work, published in Cancer Cell, demonstrated that supplementing cell cultures with D-mannose during CAR T cell expansion may improve their ability to resist exhaustion and effectively combat cancer. This approach leverages the connection between cell metabolism and immune system health, potentially leading to more effective CAR T cell therapies.
Overcoming T-Cell Exhaustion in Lung Adenocarcinoma
Shivani Srivastava, PhD, presented a strategy to improve cell therapies for solid tumors by overcoming T-cell exhaustion. Her lab found that genetically engineering CAR T cells to overexpress c-Jun while blocking PD-L1 resulted in a significant boost in CAR T cell numbers within tumors in a mouse model of non-small cell lung cancer. This approach led to near eradication of tumor cells expressing the CAR target antigen, suggesting a promising avenue for enhancing CAR T cell therapy in solid tumors.
