ECLIPSE looks to extinguish leukemia by uncovering new treatment targets

MD Anderson has created a new research platform to drive the discovery of new therapeutic agents for patients with leukemia by investigating the complex interactions and changes between cancer cells and the immune system over time.

ECLIPSE – or Evolution of Cancer, Leukemia, and Immunity Post Stem cEll transplant -- is one of the  platforms launched by MD Anderson’s Moon Shots Program® to provide unique expertise, technical support and novel infrastructure to enable impactful research projects. The Moon Shots Program is a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients’ lives.

ECLIPSE also is an important component of MD Anderson’s Therapeutics Discovery division, a unique group of clinicians, researchers, and drug discovery and development experts working to advance the next generation of impactful cancer medicines, inspired by the needs of patients and guided by unmatched clinical insight. 

Jeffrey Molldrem, M.D., professor and chair ad interim of Hematopoietic Biology and Malignancy and professor of Stem Cell Transplantation and Cellular Therapy, leads the ECLIPSE platform. He spoke with Cancer Frontline about the platform’s work and its integration within Therapeutics Discovery.

Can you describe the work of ECLIPSE and how you’re advancing the Moon Shots Program’s mission of saving patients’ lives?

ECLIPSE seeks to identify and understand the co-evolution of hematopoietic tumors and the adaptive immune response over time. Using a deep –omics approach for our analyses, we’re working to simultaneously understand this co-evolution and to identify potential target antigens and matched therapeutic receptors, either T-cell receptors or B-cell receptors.

Working in the blood stem cell transplant space, we’re striving to identify novel targets that we can leverage through our integrations in Therapeutics Discovery and the Moon Shots Program to bring impactful therapies to patients that need new treatment options.

What sets the platform apart from others doing research in this area?

We’re particularly unique in that we can use clinical patient outcomes to distinguish the relevance of a target and receptor that we identify. We have the largest sample collection anywhere on Earth, going back 22 years, of both patient and matched healthy donor cells and serum complete with clinical outcomes data. Whereas most others have samples from a static time point, we’re able to look over time and use patient outcomes to distinguish between relevant targets we identify.

Because we are doing this in the hematopoietic stem cell transplant setting,  which provides a  more target-rich environment, we can more readily distinguish actionable targets and immune receptors on T cells and B cells.

How does ECLIPSE complement the work of others in the Therapeutics Discovery division?

Within Therapeutics Discovery, we’re situated in the upstream side of discovery and development. We are fully integrated within the Biologics Development team, working to identify actionable targets that we can use to make a therapeutic.

We perform target identification and validation fully from patient material, and those receptors can be the basis for future therapies designed by either the adoptive cell therapy platform, the ORBIT platform or both.

Where have you seen success already? What projects are you most excited about?

Our first proof-of-concept was the development of a first-in-class T cell receptor (TCR)-like antibody, h8F4. Using the ECLIPSE approach, we identified the PR1 peptide, which we then validated and later developed the h8F4 monoclonal antibody against it that showed potential anti-leukemic activity. Through the support of the ORBIT platform, that molecule has now advanced to Phase I clinical testing here at MD Anderson, led by Tapan Kadia, M.D., associate professor of Leukemia. That was all done in-house and is our first success.

We have several additional TCR-like antibody programs in development now, based on targets we have identified within ECLIPSE. We have another antibody that should be ready for clinical trials in 2020.

How is your work enabled by your integration with the Moon Shots Program and the research infrastructure at MD Anderson?

We wouldn’t be able to carry our work to the clinic without our integration with ORBIT and the other Therapeutics Discovery platforms. We are highly integrated, and we designed it that way to avoid duplicative efforts,  as well as leverage complementary skills and methodologies to fulfill our mission to eliminate cancer. We have strong collaborative interaction along the entire continuum, from target discovery and validation to clinical production and testing. We even share adjacent space and equipment to facilitate close working relationships and to leverage our strengths.

Further, some of our targets may be more vulnerable to a small-molecule drug, so it’s important that we are connected closely with IACS as the small-molecule engine at MD Anderson.

Finally, several members of our Moon Shots team are focused on understanding leukemias and hematopoietic malignancies, so we’re able to learn from each other. They can utilize what we pull from our deep –omics analysis in transplant patients to better understand, for example, how leukemia evolves in the transplant setting compared with what is observed under standard treatment. We’re also able to collaborate and gain insight from these teams and what they’re advancing in the clinic to all move toward our common goal of saving patients’ lives. It’s really an invaluable effort that we’ve established here.

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