Publications by authors named "M Jose Fernandez de Sanmamed"
Immune-checkpoint inhibitors (ICIs) have improved clinical outcomes across several solid tumour types. Prominent efforts have focused on understanding the anticancer mechanisms of these agents, identifying biomarkers of response and uncovering resistance mechanisms to develop new immunotherapeutic approaches. This research has underscored the crucial roles of the tumour microenvironment and, particularly, tumour-infiltrating lymphocytes (TILs) in immune-mediated tumour elimination.
View Article and Find Full Text PDFBispecific agents targeting tumor-cell surface antigens and activating receptors on T lymphocytes are being developed for solid tumors. Effective and safe strategies depend on target specificity and at least relative tumor-tissue confinement of T-cell activation. Novel evidence suggests that constructs targeting HER2 on tumor cells with the aim of providing costimulation (signal 2) to T lymphocytes via cluster of differentiation 137 (4-1BB) are safe and can meaningfully invigorate antitumor responses in a proportion of patients.
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- Gainor and colleagues investigated the effectiveness of personalized mRNA vaccines that target neoantigens to stimulate immune responses in patients after tumor removal.
- In their study, they observed significant T-cell responses, specifically polyfunctional CD8+ and CD4+ T-cells, reacting to 20% to 30% of predicted MHC-I and MHC-II epitopes.
- The research involved 16 patients—four with non-small cell lung cancer receiving the vaccine alone, and twelve with melanoma treated with the vaccine alongside pembrolizumab in a phase 1 clinical trial (NCT03313778).
Article Synopsis
- The study focused on pairing naporafenib, a pan-RAF inhibitor, with either rineterkib or trametinib to treat patients with non-small cell lung cancer (NSCLC) and certain genetic mutations.
- Conducted on 216 patients, the research aimed to find safe and effective dosage levels, identifying recommended doses while monitoring for side effects and antitumor activity.
- Results showed dose-limiting toxicities in 16% of patients, with some achieving partial responses; the study established specific dosages that were well-tolerated along with noticeable reductions in certain mRNA levels.
Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable V600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients.
Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C).