A novel immunogenic mouse model of melanoma for the preclinical assessment of combination targeted and immune-based therapy.

Both targeted therapy and immunotherapy have been used successfully to treat melanoma, but the development of resistance and poor response rates to the individual therapies has limited their success. Designing rational combinations of targeted therapy and immunotherapy may overcome these obstacles, but requires assessment in preclinical models with the capacity to respond to both therapeutic classes. Herein, we describe the development and characterization of a novel, immunogenic variant of the BrafV600ECdkn2a-/-Pten-/- YUMM1.1 tumor model that expresses the immunogen, ovalbumin (YOVAL1.1). We demonstrate that, unlike parental tumors, YOVAL1.1 tumors are immunogenic in vivo and can be controlled by immunotherapy. Importantly, YOVAL1.1 tumors are sensitive to targeted inhibitors of BRAFV600E and MEK, responding in a manner consistent with human BRAFV600E melanoma. The YOVAL1.1 melanoma model is transplantable, immunogenic and sensitive to clinical therapies, making it a valuable platform to guide strategic development of combined targeted therapy and immunotherapy approaches in BRAFV600E melanoma.

Imaging response assessment of immunotherapy in patients with renal cell and urothelial carcinoma.

PURPOSE OF REVIEW: Recent advances in anticancer immunotherapy have revolutionized the treatment of metastatic renal cell (RCC) and urothelial carcinoma. In this review, we discuss the mechanisms of action of these new therapeutic approaches, explicate the common adverse events, and highlight different imaging-based response criteria. RECENT FINDINGS: The recent introduction of immune-checkpoint inhibitors led to substantial advances in therapy of metastatic RCC and urothelial carcinoma. Because of the distinct effector mechanisms of these new substances, atypical response patterns such as transient enlargements of tumor lesions, appearance of new lesions after therapy, no measurable decrease in tumor size, or delayed responses are observed in medical imaging studies. This indicates that the established imaging-based response assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines has shortcomings to comprehensively evaluate treatment effects. SUMMARY: While monitoring response to immunotherapy still relies on RECIST criteria, immune-related response criteria have been established to better address the imaging changes occurring under immunotherapy. Further studies with long-term follow-up are needed to properly identify and predict response after treatment beyond progression. Because of the expanding clinical use of immune checkpoint inhibitors, radiologists, urologist, and oncologists should be familiar with common imaging findings under this respective therapy.

Tolerance--is it worth it?

We are entering an exciting time in the study of immunologic tolerance. Several cellular and molecular strategies have been developed that show promise in nonhuman transplant models and these approaches are just now appearing in clinical trials. Tolerance strategies that prevent immune rejection and obviate the need for immunosuppressive medications (with inherent risk of cancer, infection, and organ toxicity) would improve both graft and patient survival. Each tolerance protocol brings its own set of associated risks. As the results of these trials become available, we must continue to evaluate their successes and failures. The balance of these outcomes will help us answer the question: "Tolerance-Is it worth it?"