New Antibody Therapy Targets Metabolic Barriers to Enhance Anti-Tumor Immune Response

A groundbreaking study by Ludwig Cancer Research has uncovered a novel approach to overcoming tumor-induced immune suppression through targeting metabolic pathways. Researchers identified that within the tumor microenvironment (TME), immune cells uptake excess lipids via the transporter protein CD36, which acts as a metabolic checkpoint hindering effective anti-cancer immunity. To counter this, scientists developed a humanized antibody named PLT012 that specifically binds to and inhibits CD36, thereby disrupting its role in lipid transport.

This inhibition restores the functionality of immune cells, particularly reversing the immunosuppressive activities of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), while reactivating effector T cells that can attack tumor cells. Experiments conducted in mouse models of hepatocellular carcinoma (HCC) and colon cancer liver metastases demonstrated that PLT012 significantly reduces tumor growth and enhances the efficacy of existing immunotherapies like checkpoint inhibitors.

Furthermore, the antibody effectively reprograms the immune environment in tumors derived from human HCC patients, indicating promising translational potential. Importantly, safety evaluations in monkeys and mice revealed that PLT012 can modulate lipid uptake without inducing autoimmune issues, underscoring its suitability for clinical development.

This research marks CD36 as a new targetable metabolic immune checkpoint and introduces PLT012 as a pioneering immunotherapy agent. Because CD36 is expressed across various tumor types with lipid-rich environments, this therapeutic strategy could have broad applications in cancer treatment. The antibody has received orphan drug designation from the FDA and is moving towards clinical trials to evaluate its efficacy in humans.

In summary, by tackling the metabolic mechanisms tumors exploit to evade immune attacks, PLT012 offers a new paradigm in cancer immunotherapy—potentially improving outcomes for patients with resistant or difficult-to-treat tumors. The findings highlight the importance of targeting tumor metabolism alongside conventional immune checkpoints, opening avenues for more comprehensive cancer treatments.

Source: https://medicalxpress.com/news/2025-04-antibody-based-drug-dismantles-metabolic.html