Cambridge Healthtech Institute’s Emily Le, PhD recently spoke with Michael Klichinsky, PharmD, PhD, Co-Founder & VP, Discovery Research, at Carisma Therapeutics about his upcoming featured presentation “CAR Macrophage Immunotherapy: A New Frontier for Innate Immunity”, to be delivered at the Targeting Innate Immunity Congress.


FEATURED PRESENTATION: CAR Macrophage Immunotherapy: A New Frontier for Innate Immunity

Our approach can overcome the hurdles of cell therapy in the treatment of solid tumors by modulating the tumor microenvironment (TME) through macrophages with key characteristics: recruitment and access to the solid tumor TME, ability to survive in the hostile solid tumor milieu, maintenance of an anti-tumor phenotype in the presence of immunosuppressive factors, capacity to selectively destroy cancer cells, and activation of an adaptive immune response by presenting engulfed tumor material.

Q. Please tell us a bit about your background and your current role.

I started out by training as a pharmacist in the PharmD program at the Philadelphia College of Pharmacy at the University of the Sciences in Philadelphia. I quickly realized the science was the most exciting part of medicine for me – so I began doing lab research at the Philadelphia College of Pharmacy and the Wistar Institute. Immediately after completing my PharmD, I joined a PhD program in Pharmacology at the University of Pennsylvania, just a few blocks down the street. I was fortunate to join the labs of Carl June and Saar Gill (they were my co-mentors) for my dissertation research, which was titled “Human chimeric antigen receptor macrophages for cancer immunotherapy”. This project was the scientific basis for the company Saar Gill and I co-founded, called Carisma Therapeutics. In my current role as the VP of Discovery, I manage the research and discovery efforts of Carisma Therapeutics.

Q. As a spin-off company from Carl June’s lab at UPenn, can you share with us your journey from the discovery stage to establishing this exciting company?

Spinning a company out of a thesis project has been an unexpected and exciting journey. I was fortunate to have fantastic mentors who supported an outside-the-box project. The University of Pennsylvania was instrumental to our success. Specifically, UPenn’s Penn Center for Innovation (PCI) helped Saar and I initiate the process of founding the company – from forming an LLC to initiating our fundraising efforts. The company grew as we raised a Seed Round and eventually a Series A in 2018, with support from a fantastic team of investors that believe in the potential for myeloid based cell therapy of solid tumors.

Q. In the spirit of this meeting Targeting Innate Immunity Congress: Differentiating Friends from Foes. Who are the “Friends” and who are the “Foes” in your CAR Macrophage Immunotherapy approach?

The friends are definitely the T cells. Part of the rationale for using macrophages is that they are professional antigen presenting cells. Our hypothesis is that our engineered CAR macrophages will traffic to the tumor, phagocytose and kill tumor cells via CAR/antigen interaction, produce cytokines/chemokines to warm up the tumor microenvironment, then directly present tumor derived antigens to T cells. The last step – antigen presentation – has the potential for leading to broad endogenous adaptive immune rejection of the tumor via the epitope spreading phenomenon. Thus, the interaction of Carisma’s CAR macrophages with endogenous T cells has the potential to amplify the therapeutic anti-tumor effect. NK cells have the potential to be Friends as well. Foes are likely the various immunosuppressive cells that can suppress the process of T cell activation – such as MDSCs, tumor associated macrophages, and regulatory T cells. We believe that adoptively transferred macrophages that are properly engineered have the potential to suppress or overcome the Foes.

Q. What is Carisma’s next step in the immunotherapy approaches/pipeline?

The next milestone for Carisma is the initiation of our first in human Phase I clinical trial. Our lead program, CT-0508, is a HER2 targeted autologous CAR macrophage that should be entering the clinic in the near future. The indication is HER2 overexpressing solid tumors, such as breast, gastric, salivary, lung, and others.

Q. Where do you think the field of innate cell therapy in oncology and other diseases is going in the next 5 years?

Despite the relatively recent success of CAR-T, the field of adoptive T cell therapy has been in development for decades. Fundamental questions around cell sources, culture methods, expansion methods, engineering methods, synthetic biology decisions, in vitro assays, in vivo assays, and many others, have been slowly answered with the academic work of probably hundreds of graduate students and post docs over the last few decades. These questions all remain to be answered in the innate cell therapy field. At Carisma we are striving to be the leaders in this field. With the help of a tremendous team of scientists at Carisma, we hope to contribute to answering some of these questions and evolve the science.


Klichinsky_MichaelMichael Klichinsky, PharmD, PhD, Co-Founder & VP, Discovery Research, Carisma Therapeutics

Michael is a co-inventor of the CAR Macrophage technology and a scientific co-founder of Carisma Therapeutics Inc. In his role as VP of Discovery Research, he oversees the research & discovery efforts of the company. Michael developed CAR Macrophages during his doctoral thesis under the co-mentorship of Saar Gill and Carl June at the University of Pennsylvania. Michael’s scientific expertise is in the intersection of immunology, synthetic biology, cancer immunotherapy, and translational pharmacology. Michael previously earned a Doctor of Pharmacy degree from the University of Sciences in Philadelphia, and a PhD in Pharmacology from the University of Pennsylvania