Patrick Hwu, M.D.
Professor and Chair
Melanoma Medical Oncology
University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd, Unit 430,
Houston, TX 77030
TRIUMPH Melanoma Project Title: Generate a response against cancer using combinations of targeted and immunotherapy.
Objective: Determine rational therapeutic approaches to treat patients with metastatic melanoma utilizing melanoma mouse models and/or patient blood and tissue samples.
Surgery and chemotherapy have long been considered standard of care for metastatic melanoma, however the response rates for those treatment modalities remain dismally low (about 10 – 12%). Two new therapeutic approaches for melanoma (immunotherapy and targeted therapy) are gaining critical acclaim and acceptance. We have had response rates of over 45% in some of our early studies with immunotherapy and targeted therapy. This being said, we are still in the process of determining why, for immunotherapy, some patients have remarkable and durable results while others do not. Also, we have seen amazing initial results for some targeted therapies with almost immediate resolution of symptoms and tumors. However, such results have not proven to be durable for most patients. Further study and rational combinations of immune agents as well as targeted therapies may be essential to gain the fullest potential of personalized therapies.
Adoptive T-cell therapy (ACT) has tremendous potential for the treatment of patients with advanced cancers. We have been successful in identifying a patient’s own cancer killing cells (T-cells) and expanding those tumor-reactive T-cells to large numbers in the lab. Once they have multiplied to therapeutic numbers, these cells are then reinfused back into the melanoma patient from whom they were harvested. This revitalized force of soldier cells have the potential to aggressively and effectively wipe out the tumors they encounter. This has been a major and exciting laboratory-to-clinic undertaking, and as mentioned above has allowed us to help many patients who had limited options. We are now looking very close at our survivors who have been very kind in offering us blood and/or tumor samples to examine in our lab. One very important laboratory project we have underway is to look closely at the T-cells that have survived which remain primed waiting to attack any future cancer. Our objective is to determine how these cells correlate with patient responses, and to use what we learn to make ACT better.
Targeted therapy focus
The treatment of melanoma is entering into a new era of personalized therapy based on an improved understanding of the molecular causes and diversity of these cancers. We have gained a more focused direction from our molecular studies which have shed new light on the strategies needed to facilitate the development of more effective personalized targeted cancer therapies. We have had success in using specific drug combinations to shut down pathways that have halted the progression of melanoma for patients with specific molecular characteristics, however finding methods to make these results long lasting will take concerted effort. In addition, gaining the data needed to have new drugs approved as standard of care is a time consuming, but worth-wild effort.
Combinations of the best of both genres
The rational combination of the two disciplines mentioned above, target therapy and immunotherapy, are expected to result in substantial gains for our patients. It is now possible to combine immunologic agents such as TIL, CpG, anti-CTLA4 Interferon alpha, Interleukin-II, anti-CD40, and anti-41BB. Notwithstanding, targeted therapeutic agents such as MEK and BRAF inhibitors have shown remarkable results for some patients. This is a very exciting time to be engaged in melanoma research.