Rizwan Romee, MD
Physician, Dana-Farber
Associate Professor of Medicine, Harvard Medical School
As their name implies, natural killer (NK) cells are immune cells with an intrinsic propensity to kill cancer cells and are of high interest in the cancer immunotherapy field. However, they can’t always get into the tumor microenvironment to do the job, particularly in solid cancers. One strategy for boosting the effect of NK cells is to create what are called NK-chimeric antigen receptor (CAR) therapies, or NK-CARs, to get NK cells to cancer cells and destroy them. CAR therapies work by genetically altering a part of the immune system to fight cancer.
The Accelerator is funding a new NK-CAR approach from the laboratories of Assoc. Prof. Rizwan Romee, MD, director, Haploidentical Donor Transplantation Program, and Assoc. Prof. David Barbie, MD, associate director, Robert and Renée Belfer Center for Applied Cancer Research. The technique is aimed at improving the cancer-seeking and killing ability of NK-CAR therapies by harnessing the properties of the STING — or stimulator of interferon genes — pathway that naturally attracts NK to cancer cells.
“Our novel genetic manipulation allows us to create what are ‘STING seeker’ NK cells and NK cell CARs which are much better at gaining entry to tumors and killing solid tumors,” says Dr. Romee. Currently, STING agonists need to be injected directly into tumors, representing a particularly obvious dilemma in the face of metastatic disease.
This new approach is based on the hypothesis that exogenous STING agonists are not necessary to trigger STING activation. Instead, the team’s approach is to take advantage of the STING mechanism by genetically modifying NK cells into STING seekers. The improved NK-CAR therapies should reach cancer cells more easily, survive longer in the harsh tumor microenvironment, and lead to better cancer cell death.
NK cell CARs which are much better at gaining entry to tumors and killing solid tumors.
Rizwan Romee, MD
Contributions from Mubin Tarannum, PhD, post-doctoral fellow and Romee lab manager allowed the team to test the activity of the engineered NK cells in various in vitro and in vivo cancer models. Moving forward, with Accelerator support the researchers plan on new studies in mouse models of some of the toughest solid cancers to treat, including lung (mesothelioma and NSCLC), ovarian, and pancreatic tumors. They will evaluate the modified NK-CARs alone and in combination with a STING agonist.
The team also plans on investigating their modified NK-CARs in patient-derived organoids – cultures of tumor cells derived from patients – that mimic the biological characteristics of real human tumors.
Team Members
David Barbie, MD
Associate director, Robert and Renée Belfer Center for Applied Cancer Research
Associate Professor of Medicine, Harvard Medical School
