Ariel Isser

Decades of research in cellular therapies for cancer have focused on modulation of cytotoxic — CD8+ — T cells, the immune system’s professional killers. In the Schneck lab, we have sought to advance these cell therapies to the clinic through development of acellular platforms that promote CD8+ T cell antitumor activity. That said, a recent appreciation for the pivotal role that helper — CD4+ — T cells play in therapeutic cancer immune responses has motivated us to generate nanoparticle technologies targeting both effector and helper functions of CD4+ T cells. In our recent work, we showed that our nanoparticles can expand rare antigen-specific murine and human CD4+ T cells. Intriguingly, unlike with other traditional stimulation platforms, CD4+ T cells activated with these nanoparticles demonstrate cytotoxic activity, a phenotype that has been observed almost exclusively in vivo, allowing us to probe the etiology of this uncommon but clinically relevant cell subset. Additionally, using a nanomaterial approach to spatially control the proximity of CD4+ and CD8+ T cells during activation, we demonstrated that help signals from CD4+ T cells could be relayed to CD8+ T cells, in turn enhancing CD8+ T cell memory formation, function, cytotoxicity and antitumor activity. These findings illustrate several ways in which CD4+ targeted nanotechnologies can bolster current approaches to cancer immunotherapy.

Questions & Answers

Why did you choose Johns Hopkins for your work? I was excited about working in an environment that nurtures both scientific rigor and clinical translation. During my visit, I was also struck by the eagerness of professors and students alike to share their work and their ideas. Indeed, I feel privileged to have trained in such a highly collaborative, unselfish environment at Hopkins. What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received? I am honored to be the recipient of such a prestigious award and to be recognized within the same forum where so many of my scientific role models are currently or were previously recognized. I am humbled to see this project recognized, especially given the many obstacles and sources of doubt that have challenged it from inception. I feel a special, close connection with the David Yue Research Award. Although I never had the privilege to meet Dr. Yue, since hearing about his legacy during my first visit to Hopkins, I have felt drawn to his infectious, child-like fascination for science and have turned to his quote about the privilege of scientific discovery time and time again as a wellspring of inspiration when encountering failures in lab. I hope to honor Dr. Yue’s life and legacy throughout my career in biomedical research. What contributed to your project’s success? (Special skills, interests, opportunities, guidance, etc.) Nothing contributed more to my project’s success than Dr. Schneck, who took a chance on me, allowing me to pursue a risky project outside of the lab’s traditional focus and connecting me to all of the right collaborators and resources to make it happen. I am also indebted to all of my collaborators, especially in Dr. Jamie Spangler’s and Sharon Gerecht’s labs, for the support and faith they showed in the project and in me. This project would certainly not have happened if not for their time, effort, expertise, materials and ideas. Lastly, this project’s success was due to support from the NIH [National Institutes of Health] Tetramer Core Facility, my mentees and my wife. What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Hopkins? Young Investigators’ Day is a fantastic way to celebrate the scientific contributions of Hopkins trainees. As someone who has spent most of his graduate career looking up to previous YIDP honorees, I can personally attest to how inspirational and motivating this ceremony is! What has been your best/most memorable experience while at Hopkins? My most memorable experience at Hopkins was attending Gregg Semenza’s press conference at Hopkins after he won the Nobel Prize in Physiology. Not only was it moving to be at such a historic moment for the university, but I was particularly inspired by all of the Hopkins pride Dr. Semenza exuded and that was palpable throughout the auditorium during his speech. It made me feel incredibly privileged to have had the opportunity to study here. What are your plans over the next year or so? Graduating, looking for faculty positions, etc.? I plan to graduate in May, and I am currently applying to immuno-oncology R&D positions. Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences? I am one of four boys and I have five nephews — no nieces. Also, my wife and I are both left-handed. Our families are naturally curious whether our children are all going to be left-handed males. Also, my dad has been training me since a very young age to sing cantorial music, which makes me one of a very small number of Modern Orthodox Jews on the planet who are, somewhat, versed in the art of cantorial music.