
Antoni Ribas, M.D., Ph.D.
Bio
Antoni Ribas, M.D., Ph.D., conducts laboratory and clinical research focused on malignant melanoma, an aggressive form of skin cancer for which few effective therapies exist. He is working to understand how a patient’s own immune system can be harnessed to attack melanoma. This research informs the development of new immunotherapies that utilize the body’s natural defenses to fight cancer.
Ribas’ laboratory has made major advancements in the treatment of melanoma. Most significantly, he led the clinical program that demonstrated the effectiveness of the drug pembrolizumab (marketed as Keytruda), which ushered in a paradigm shift in the way melanoma is treated. The drug blocks a protein called PD-1 that sits on the surface of immune cells and keeps them from recognizing and attacking cancer cells. This was the first of the class of PD-1 blocking antibodies to be approved by the Food and Drug Administration for the treatment of any cancer. Keytruda is now used in the treatment of inoperable, metastatic melanoma, non-small cell lung cancers and other malignancies including Hodgkin’s lymphoma.
Ribas is conducting several clinical trials of cutting-edge treatments including both immunotherapies and targeted stem cell-based therapies. In 2017, he launched a first-of-its-kind trial that involves genetically engineering blood-forming stem cells to produce cancer-fighting T cells to treat melanomas and sarcomas and later multiple myeloma. The clinical trial involves a dual approach intended to provide patients with both short and long-term immune responses to their cancer. This is accomplished by giving patients modified blood-forming stem cells and modified mature T cells in a single transplant. Upon transplant, the modified mature T cells begin fighting the cancer immediately, while the modified blood-forming stem cells work to generate an on-going supply of new modified T cells, resulting in a lasting immune response to the cancer.
Ribas also studies how the immune system responds to and develops resistance to immunotherapies, and how combination therapies may be used to overcome treatment resistance. One such treatment the Ribas lab is evaluating combines pembrolizumab with a targeted therapy that blocks a protein that leads to mutations in the BRAF gene. The BRAF gene makes a protein called B-RAF, which is involved in cell communication and growth. When BRAF genes are mutated, they can increase the growth and spread of cancer cells; approximately one‐half of all patients with melanoma have mutations in the BRAF gene.
An additional area of focus in the Ribas lab is molecular imaging and advanced monitoring of the immune system. Ribas and his team utilize molecular imaging technology such as PET scans to investigate and understand precisely how novel immunotherapies work on a molecular level. They aim to use these technologies to guide and evaluate new therapeutic strategies for melanoma.
Ribas earned both his medical and doctoral degrees from the University of Barcelona in Spain. He completed an internship and residency at Hospital Vall d'Hebron and fellowships in surgical oncology and hematology/oncology at the UCLA David Geffen School of Medicine. He is an elected member of the American Society of Clinical Investigation.
Publications
- Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapyPublished in Cell on Tuesday, November 16, 2021
- Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonistPublished in Nature on Friday, January 31, 2020
- Multi-stage Differentiation Defines Melanoma Subtypes with Differential Vulnerability to Drug-Induced Iron-Dependent Oxidative StressPublished in Cancer Cell on Monday, May 14, 2018
- Mutations Associated with Acquired Resistance to PD-1 Blockade in MelanomaPublished in The New England Journal of Medicine on Thursday, September 1, 2016
- PD-1 blockade induces responses by inhibiting adaptive immune resistancePublished in Nature on Wednesday, November 26, 2014
- T-Cell Immunotherapy: Looking ForwardPublished in Molecular Therapy on Wednesday, September 10, 2014
- HSV-sr39TK Positron Emission Tomography and Suicide Gene Elimination of Human Hematopoietic Stem Cells and Their Progeny in Humanized MicePublished in Cancer Research on Friday, July 18, 2014
- Adoptive Transfer of MART-1 T-Cell Receptor Transgenic Lymphocytes and Dendritic Cell Vaccination in Patients with Metastatic MelanomaPublished in Clinical Cancer Research on Friday, March 14, 2014
- Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in MelanomaPublished in New England Journal of Medicine on Thursday, July 11, 2013
- Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer ImmunotherapyPublished in Cancer Discovery on Thursday, March 21, 2013
- Allelic Exclusion and Peripheral Reconstitution by TCR Transgenic T Cells Arising From Transduced Human Hematopoietic Stem/Progenitor CellsPublished in Molecular Therapy on Tuesday, February 5, 2013
- Glucose Deprivation Activates a Metabolic and Signaling Amplification Loop Leading to Cell DeathPublished in Molecular Systems Biology on Tuesday, June 26, 2012
- Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cellsPublished in PNAS on Monday, November 28, 2011
- Differential Sensitivity of Melanoma Cell Lines with BRAF V600E Mutation to the Specific BRAF Inhibitor PLX4032/RG7204Published in Journal of Translational Medicine on Tuesday, April 20, 2010
- Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticlesPublished in Nature on Sunday, March 21, 2010
- Imaging CTLA4 Blockade-induced Cell Replication with [18F]FLT PET in Patients with Advanced Melanoma Treated with TremelimumabPublished in The Journal of Nuclear Medicine on Thursday, February 11, 2010
- Immune Rejection in a Humanized Model of Murine Prostate CancerPublished in Anticancer Research on Monday, February 1, 2010
- A phase II clinical trial of nab-paclitaxel in previously-treated and chemotherapy naive patients with metastatic malignant melanomaPublished in Cancer on Friday, January 1, 2010
Honors & Affiliations
Honors
- President-Elect, American Association for Cancer Research, 2019
- Lloyd J. Old Award in Cancer Immunology, American Association of Cancer Research-Cancer Research Institute, 2018
- Great Immigrant Award, Carnegie Corporation, 2018
- Doctor Honoris Cause, University of Buenos Aires, Argentina, 2017
- Richard and Hinda Rosenthal Memorial Award, American Association of Cancer Research, 2016
- Member, Royal Academy of Medicine of Catalonia, 2015
- Outstanding Investigator Award, National Cancer Institute, 2015
- Physician of the Year, Melanoma International Foundation, 2013
- Outstanding Research Award, Society for Melanoma Research, 2013
- Elected member, American Society of Clinical Investigation, 2009
Affiliations
- Board of Directors, American Association for Cancer Research
- American Society of Clinical Oncology
- American Association for Cancer Research
- Chair, Melanoma Committee, SWOG Cancer Research Network
- Advisory Board, UCLA General Clinical Research Center
- UCLA Jonsson Comprehensive Cancer Center
Funding
Ribas’ work is funded by the California Institute for Regenerative Medicine, the National Institutes of Health, the Parker Institute for Cancer Immunotherapy, Stand Up to Cancer, the Caltech-UCLA Joint Center for Translational Medicine and the UCLA Broad Stem Cell Research Center.
Videos
Clinical Trials
- Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) and Peripheral Blood Stem Cells (PBSC) After a Myeloablative Conditioning Regimen, With Administration of Interleukin-2, in Patients With Advanced Malignancies
- Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) and Peripheral Blood Stem Cells (PBSC) After a High Dose Melphalan Conditioning Regimen, With Administration of Interleukin-2, in Patients With Multiple Myeloma