Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer
Menée sur une patiente atteinte d'un cancer métastatique du sein HR+ réfractaire aux chimiothérapies, cette étude met en évidence une régression tumorale durable et complète après un traitement combinant interleukine IL-2, inhibiteur de point de contrôle immunitaire et transfert adoptif autologue de lymphocytes intratumoraux ciblant quatre protéines mutées immunogènes (SLC3A2, KIAA0368, CADPS2 et CTSB)
Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations—such as melanoma, smoking-induced lung cancers and bladder cancer—with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins—SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.