Cancer is caused by genetic changes (errors), making every cancer unique. Nevertheless, cancers share features that allow them to be grouped into categories or “subtypes.” A tumor’s subtype strongly influences its behavior, including growth rate, likelihood of responding to one therapy versus another, and probability of relapse. Knowing each tumor’s subtype could thus help determine which therapy is best for a give a patient, a concept known as “Precision Medicine.” Currently, subtype can only be determined by in-depth sequencing of tumor tissue, and thus it is not routinely determined in clinical practice.
The goal of this proposal is to develop a rapid, non-invasive, and inexpensive way to determine tumor subtype from a blood test. This is called “liquid biopsy,” and it is playing an increasingly important role in cancer care. Because liquid biopsies are non-invasive (i.e. they do not require surgery or other procedures), samples can be obtained repeatedly over a course of therapy, allowing better clinical decisions to be made.
Colorectal cancer (CRC) is the second-leading cause of cancer death in the United States, where it has a disproportionately lethal effect on African-Americans. Recently, a consensus panel concluded that the disease has four major subtypes based on patterns of gene expression (which genes are “on” or “off” in the tumors). In this proposal, we will use these definitions to perform subtyping from liquid biopsies. In the future, the approaches we will develop here will be applicable to all cancers, not just those affecting the colon and rectum.
Funded by the Dick Vitale Gala in Memory of John Saunders
Immunotherapy has given hope to many patients with previously incurable cancers. One of the strongest new immunotherapy techniques is CD19-targeted cell therapy. This is a method of engineering T cells from a patient to attack their own cancer. B-ALL, a type of leukemia, is the most common cancer in kids. In B-ALL, CD19-targeted cell therapy has put over 90% of relapsed patients into remission within a month of receiving these engineered T cells. One problem is that some patients’ cancers learn to hide the CD19 target that these engineered T cells see. The lack of the target allows the cancer to hide from the T cells and come back. This can happen in more than 20% of patients. With this grant, we will explore an alternative target called CD22. CD22 is on more than 90% of B-ALL cells. We will use a combination of CD19-targeted T cells and a drug called inotuzumab that attacks CD22 to prevent the cancer cells from coming back, even if they can hide the CD19 target. We will also develop T cells to target CD22. First, we will move forward with a combination approach using the CD19 cells and the CD22 drug in B-ALL patients. Later, we may use T cells against both CD19 and CD22. Currently, bone marrow transplant is the best option for kids with relapsed disease, but this comes with many risks. As we increase the number of patients remaining in long-term remission with these cell therapies, we can see a future where fewer patients need to undergo the risks of bone marrow transplant.
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