Dr. Carl H. June
In an interview with the ASCO Daily News, Dr. June commented on the personal significance of this recognition and credited his colleagues at the University of Pennsylvania, his family, and the patients who volunteered to participate in clinical trials.
“I am honored to be receiving an award named after Dr. Karnofsky, who made so many discoveries that are still used in our daily practice,” Dr. June said. “I’m very proud to represent the field of cancer immunotherapy in general, and those developing CAR-T cells in particular, in accepting this award, which symbolizes the recent advances and pending [U.S. Food and Drug Administration] approvals of targeted therapies of cancer using engineered T cells.”
Early Beginnings in Adoptive Immunotherapy
Dr. June’s early beginnings in cancer immunotherapy were marked by an accidental finding that led to an unexpected turn in his research. In 1992, his postdoctoral student Dr. Bruce Levine was working on developing a T-cell culture system for HIV but repeatedly failed to isolate viral particles from T-cell cultures of patients with late-stage HIV/AIDS. Puzzled and frustrated by his student’s inability to perform this straightforward task, Dr. June repeated the experiment, only to obtain the same results.
His team later attributed the absence of viral particles in T-cell cultures of patients with HIV to the downregulation of CCR5, the HIV-1 co-receptor on CD4 cells.1 This accidental finding sparked Dr. June’s interest in adoptive transfer of T cells in patients with HIV/AIDS and resulted in two landmark publications in Science.
“Chance can have a large determination in career paths and, in my case, is perhaps best remembered by the quote from Yogi Berra, who said, ‘When you come to a fork in the road, take it,’” Dr. June said.
Adoptive Immunotherapy for Cancer and HIV Infection
In the past decade, Dr. June’s work has been focused on studying the potential use of adoptive immunotherapy for cancer and HIV infection. More specifically, his team spearheaded the introduction of gene-modified T cells as treatment for patients with HIV and cancer. Dr. June explained that the immune system suffers damage in patients with cancer that is not unlike that of patients with HIV/AIDS, which makes the simultaneous study of these two seemingly unrelated diseases useful.
“Studies with engineered T-cell therapies in [patients with] HIV have informed the field by advancing cancer immunotherapies,” Dr. June said. “It is instructive to recall that Timothy Brown, aka ‘the Berlin Patient,’ is the only person among the 40 million people infected with HIV who has been shown to be cured. This occurred when he also developed leukemia, and his leukemia treatment with a bone marrow transplant cured him of HIV and leukemia.”
Conducting research in cancer immunotherapy and HIV in parallel has provided invaluable insights to researchers in the field. In July 2014, for remarkable treatment responses achieved in more than 100 patients with acute and chronic leukemia treated with a chimeric antigen receptor in T cells redirected to CD19 (CART-19), Dr. June’s approach received the U.S. Food and Drug Administration’s (FDA) Breakthrough Therapy Designation status. This was the first time that an academic research center had received such a prestigious recognition.
Extending the Application of Engineered T Cells
Over the past decade, the field of CAR therapies has grown tremendously, with the main focus being on CAR-T cell–based therapies for leukemia. According to Dr. June, the outlook for T-cell–based cancer therapies is bright.
“We are at a tipping point, where the validation of the field of cancer immunotherapy with engineered T cells has just occurred,” he said.
Dr. June is hopeful that this validation will propel the field further and extend the application of therapies based on engineered T cells to cancers beyond leukemia.
“During the coming decade, the major challenge to the field is to extend the benefits of CAR-T cells to a broader field of patients with cancer beyond those with leukemia,” he said. “I imagine that this will involve further refinements in the design of engineered T cells and learning how to use combinations of targeted therapies and immunotherapies to avoid the development of resistance.”
Over the course of his career as an oncology researcher, Dr. June has learned to seize opportunities that come his way, even if they present themselves in the form of unexpected research results. By turning accidents into breakthroughs, he has joined the list of oncologists whose work will continue to profoundly impact the field for years to come.
His award lecture on June 3 will provide an overview of the field of cancer therapy using engineered T cells, as well as a summary of clinical trials leading to FDA approval of CD19 CAR-T cells for leukemia. He will conclude his talk with a synopsis of research on the new approaches in this rapidly growing field, beyond leukemia.
–Jasenka Piljac Žegarac, PhD