Tumor Immunology & Immunotherapy Group

Immunotherapies exploit the immune system to attack cancer. Clinical studies have shown that immune checkpoint inhibitors and T-cell-based therapies can mediate tumor regression in patients with metastatic disease. Thus, in addition to surgery, radiation therapy and chemotherapy, immunotherapy has become the fourth pillar of anti-cancer therapy. Our group focuses on better understanding the naturally occurring T-cell response to cancer and establishing ways to exploit these antitumor responses to develop more effective, powerful, and personalized immunotherapies against cancer.

Accumulating evidence supports that neoantigens play an important role in the clinical efficacy of cancer immunotherapies. Thanks to the support received from the Fundación BBVA’s Comprehensive Program of Cancer Immunotherapy & Immunology – CAIMI, as well as other funding agencies, and through our group’s long-standing collaboration with Elena Garralda, Principal Investigator of VHIO’s Early Clinical Drug Development Group, and Director of our Research Unit for Molecular Therapy of Cancer (UTIM) – CaixaResearch, we received authorization from the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS – Spanish Regulatory Agency) in May 2021 to initiate a phase I clinical trial to test the safety and tolerability of neoantigen-selected TILs.

In this ongoing clinical trial we are using a highly personalized approach (see Figure) to screen for T-cell mediated recognition of mutated antigens using autologous antigen presenting cells that can process and present in all the potential human leukocyte antigen (HLA). In this pilot clinical study funded by the Instituto de Salud Carlos III – ISCIII (Carlos III Health Institute), we aim to treat up to 10 patients with epithelial cancers and melanoma refractory to standard therapies. By enriching for neoantigen-reactive lymphocytes, we hope to extend the efficacy of TIL therapy beyond melanoma.

Our group’s work has demonstrated that tumor-reactive T cells can frequently be detected circulating in the blood of cancer patients, regardless of the specific tumor type. The ability to track and monitor tumor-reactive CD8+ and CD4+ T cells in blood has tremendous therapeutic potential, but it is more challenging due to their lower prevalence. Our group has contributed to defining a phenotypic signature that can guide the identification and enrichment of tumor- and neoantigen-reactive T cells from the blood of cancer patients and we aim to leverage this to develop minimally-invasive T-cell therapies to treat cancer patients. In addition, we now aim to conduct extensive profiling of the peripheral blood T-cell response at the single cell level in patients treated with immune checkpoint inhibitors to better understand the determinants of response.

In addition to the above-mentioned, our group is also interested in developing high-throughput technologies to better understand the landscape of tumor antigens that render tumors susceptible to immune attack, shared neoantigens as well as mechanisms of resistance to T-cell cytotoxicity.