Chrystal M. Paulos, PhD

Biography

Chrystal M. Paulos, PhD, is a Tenured Associate Professor at Emory University in the Department of Surgery with a joint appointment in the Department of Microbiology and Immunology. She has a leadership role within the Winship Cancer Institute as the Director of Translational Research for Cutaneous Malignancies. Dr. Paulos is also a faculty member in the Cancer Immunology Program at Winship and provides extensive service to the Cancer Biology Graduate Program as the Curriculum Chair and member of the Program’s Executive Committee. She holds an endowed chair titled the “David M. Lawson MD Professor of Cancer Research” to recognize her accomplishments and lend continued support to her team’s mission to advance immunotherapy. 

Dr. Paulos earned her PhD in Chemistry from Purdue University in 2004. She trained under the mentorship of Dr. Phil Low, studying new ways to target folate receptors with small molecules to treat cancer. She subsequently completed two postdoctoral fellowships. She first trained at the NIH with Dr. Nick Restifo (2004-2008). Here she investigated how the microbiome impacts adoptive T cell transfer (ACT) therapy against melanoma. Next, Dr. Paulos trained as postdoctoral fellow at Penn with Dr. Carl June (2008-2011). Her research focus was on deciphering mechanisms by which co-signaling molecules CD28 and ICOS regulate the antitumor activity of human CAR T cells. Prior to joining Emory University in her current role, Dr. Paulos was a tenured faculty member and Co-Leader of the Cancer Immunology Program at the Hollings Cancer Center at MUSC (2011-2020). 

The objective of Dr. Paulos’ research program is to develop novel T cell-based therapies for patients. Her team seeks to identify mechanisms underlying protective immunity to tumors, with an emphasis on ACT therapy. Her work embraces both basic and translational science to better understand and adapt human T cells for therapy. These efforts are accomplished via both early phase clinical studies in patients and complemented by mechanistic studies in relevant mouse models. The Paulos laboratory has contributed vast insight into various strategies of how to mount T cell memory responses to tumors. As evidence of this, her lab has been productive, with over 100 high-impact articles that exceed 11,000 citations. Dr. Paulos and her teams’ studies on cellular therapies are funded by Institutional, National, Federal, and Industry grants. The Paulos lab uses cutting-edge mouse tumor models to address the some of the most critical questions facing the field. Importantly, she also works closely with basic immunologists and physician scientists, in the context of clinical trials in patients. 

Dr. Paulos is an advocate for the advancement of her trainees. She is an expert at teaching her mentees how to write compelling research grants, evidenced by the fact that many on her team (~17 graduate students, postdoctoral fellows, research specialist, and clinical residents) have been awarded funding from the NIH, American Cancer Society, Melanoma Research Alliance and/or other foundations over the years. Not only is it important to her to create a diverse/inclusive research environment for her mentees to thrive, but she also works to empower them to develop a strong voice to advocate for themselves and to reach their personal aspirations. 

Dr. Paulos is an advocate for women in science in all stages of their career. Her team works with the Winship Woman in Science program to help instill excitement in female high school students about careers in research. She has worked closely with many new female faculty, both basic immunologists and physician scientists, to advance various aspects of their careers. Dr. Paulos has invited many well-known female immunologists to present at the Elkin Lecture at Emory. She is an engaged member of many organizations that promote woman in science: American Association of Immunologists (Speaker Organizer) and SITC (Women in Cancer Immunotherapy Network Leadership Institute). 

Dr. Paulos became involved in the SITC organization in 2006 as a postdoctoral fellow. Since that time, she has participated in many national meetings. In 2012, as an independent investigator, her trainees began presenting posters or giving podium talks on their research work. It was then that Dr. Paulos became very involved in SITC, including being a co-chair at the various meetings focused on a range of topics over the years, including cytokines in T cell biology to advances in adoptive immunotherapy. From 2015 and onward, Dr. Paulos has worked with local experts to educate clinicians on emerging immunotherapy in a SITC program titled Advances in Cancer Immunotherapy™ (ACI). Starting in 2020, she became an executive ACI committee member to continue to grow the program to educate the medical oncologists on emerging therapies for patients. In 2018, Dr. Paulos became a SITC Champion, where she continually works with SITC leadership to address the needs in the field and provides communication between the society and her home institution. Most recently, Dr. Paulos has become actively involved in the Awards Review Committee and the Cancer Cell Therapy Taskforce. Also, she became an organizer for the SITC Cancer Immunotherapy Winter School (2024-2027), a program, taught by leading experts, which provides a deep understanding of the core principles of tumor immunology and immunotherapy. Dr. Paulos is enthusiastic about her research, her trainees, and bolstering the growth of SITC for years to come.

Chrystal M. Paulos, PhD

SITC Election Platform Statement


What are the two or three critical issues facing the field of cancer immunotherapy?

Immunotherapy has made a lasting positive impact on the lives of many patients diagnosed with cancer. Several individuals have experienced notable responses—and even cures—due to the discovery and implementation of cutting-edge therapies that direct immune responses to the patient’s tumor. Those therapies include (but are not limited to) vaccines, oncolytic viruses, novel cytokine therapies, immune checkpoint blockade (ICB) therapy and innovative adoptive cell transfer (ACT) therapies. Yet there remains room for improvement, as many patients are unresponsive to immunotherapy approaches or relapse. These therapies can also mediate toxic side effects in patients. Another significant concern is the fact that these treatments can often be cost prohibitive, thus rendering them less accessible to patients who live in rural areas, have limited financial resources and/or live in developing countries. There is an urgent need to safely and strategically advance immunotherapy to serve more patients. To do so, the SITC organization must empower teams of basic immunologists, physician scientists and industry partners to tackle some of the biggest questions in our field:

A. Why do some patients respond to immunotherapy while others do not respond?

Our field has uncovered factors that inform the likelihood of a patient’s ability to benefit from immunotherapy, including clear associations between improved outcomes to immune checkpoint blockade (ICB) with more T cells in the tumor and a greater mutation burden in the malignancy. However, we still need to do better. By exploiting multi-omics and bioinformatics approaches with teams of basic immunologists and translational scientists, we can more accurately define what type of therapy will best work for each individual patient, as well as continue to uncover key factors underlying why some patients benefit from IO agents, while others do not. This work will benefit efforts in the field to develop robust biomarkers for maximizing clinical benefit, while sparing toxicities in others with lower likelihood of responding. We must also find ways to better prepare our patients with novel therapies that can sustain durable immunity, such that follow up approaches, including ACT, oncolytic viruses, and agents that augment the innate immune response that can be used to effectively treat a patient that relapses.

B. How can we quickly generate cellular therapy that can safely and more cost effectively treated patients? 

Adoptive cell therapies have proven highly effective for patients with certain advanced cancers. Yet, the time it takes to manufacture these therapies means some patients will require additional bridge therapies or experience disease progression. Moreover, protocols needed for expansion of TILs to large enough numbers to infuse into patients can often result in suboptimal cellular products that are poorly functional, terminally differentiated and/or even exhausted. Similarly for CART or TCR-based therapies, more refined methodology to expand cells could benefit functional properties of the final products. There are many talented scientists in the academic, government and industry settings that are devising ways to generate immune cells with enhanced performance using small molecules, cytokines, and other clever genetic strategies. Moreover, there are many groups investigating new ways to make cellular therapies faster and thus more accessible to patients. Our team and others have reported on the production of a potent adoptive T cell therapy through novel short expansion protocols as few as 1-4-days. We found that shortening the manufacturing process can generate fewer potent CD4 T cells faster, but with far more potent tumor-killing abilities. Many investigators are now demonstrating that short-term, expanded TILs or CAR products can be more intrinsically therapeutic. Our field is now showing that likely far fewer, high-quality immune cells would be needed, therefore reducing the amount of time needed to expand the cells. If we can accomplish this, then we can also reduce the cost of the therapy. Using fewer cells might also decrease the chances of toxic side effects, including a cytokine storm, which could open the therapy to more patients as well. By exploiting approaches that cut down on manufacturing time, this approach could have broad and far-reaching impact for using various types of cellular therapy at multiple institutions around the world. Theoretically, this approach could be used for quickly generating effective NKs, TILs and CAR/TCR T cells products for patients across both solid and hematologic tumors. Coupling this shortened expansion with an upfront selection process could be more fruitful, saving both time and money by avoiding a scenario that could typically take up to 1 or 2 months. If the proper cells are selected out, as our research has shown, then cell expansion can be shortened dramatically. The in-situ generation of antigen-specific T cells using novel mRNA approach is also a very exciting field of study, as it could also dramatically reduce the cost of this form of therapy and reach a larger patient population. As many scientists are now working on innovative ways to improve cellular therapy, as an executive member, I would strive to empower them by acting as a liaison and advocate within the SITC organization to champion creative ways for promoting regular interactions between investigators at all career stages across academic, government and industry settings to take things to the next level. 

What is Your Vision for SITC?

SITC is a prominent leader in helping the brightest minds communicate their newest and most important findings to the cancer immunotherapy field. The SITC platform has helped many basic researchers, physician scientists, and translational immunologists learn how to leverage the immune system to target tumors and to thus treat more patients with cutting edge therapies. SITC has inspired many networks of talented researchers and clinicians to work together around common objectives, all united with the goal to cure cancer and to manage diseases more safely. SITC will continue to foster new and established investigators to advance their most exciting preclinical findings into the clinic to treat patients with cancer at various types of national and international forums and through internal grant mechanisms. I am honored to be a part of this program and I am passionate about working with the SITC executive team to advance cancer immunotherapy. I am eager to help young investigators advance their career and provide them with advice about grant writing, recruiting talented people into their lab and how to navigate promotion and tenure at their institutions. This can be accomplished with efforts invested in creating retreats focused on these goals for basic researchers, physician scientists and translational immunologists. I would also love to work with early career scientists in the organization on how to both navigate mechanisms and share experiences related to “climbing the ladder” to professional advancement. I am also eager to share my expertise with investigators at all stages surrounding how to protect intellectual discoveries that could lead to patents or even companies based on their ideas. Working with other women in the SITC WIN Leadership Institute program, I would love to create a session focused on empowering women scientists by improving interactions between industry, academic and government partners. I am also very fortunate to attend the annual Immunotherapy Bridge meeting, sponsored in part by SITC and would love to expand the reach of both US and international scientists via this and other mechanisms. SITC does an exceptional job of ensuring a presence at other oncology-focused meetings and cross interacting with ASCO, AACR and other foundational meetings. I would like to play a role in further promoting awareness of SITC and maintaining its reputation as an authority on cancer immunotherapy. I truly feel that we can make a profound difference in the lives of patients by working together in a united front against a common enemy of cancer.