Project Term
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Project Summary
We have discovered that the tumor cells of the vast majority of follicular lymphoma cases have a unique tumor-specific feature in their major receptor. This is an essential modification that allows lymphoma cells to capture local support from tissue cells. Our investigation will add diagnostic and prognostic value and provide a new target for therapy. We will develop a new antibody approach which will improve the potency of existing treatments.
Lay Abstract
Follicular lymphoma (FL), the most common type of “low-grade non-Hodgkin lymphoma”, is an indolent blood cancer for which there is no cure. Although responses are often observed, early intervention using current treatments is not recommended because these treatments are toxic and not able to eradicate FL. Therefore FL will be bound to progression and some patients will experience transformation to an aggressive lymphoma type, which is often resistant to existing treatments. Therefore, better and less toxic treatment strategies for long-term control or early eradication of FL are needed.
In this program we propose to further characterize a founding mechanistic vulnerability of FL and understand how to place an antibody therapy against it in the treatment strategy of FL. This vulnerability not seen in normal B cells and is therefore a unique tumor-specific feature, essential for the FL cells to interact with multiple immune cells and thrive in their microenvironment. This feature is a sugar that we have called sIg-Mann.. sIg-Mann is expressed early by the tumor cells in the vast majority of FL cases and is maintained during their entire natural history including after transformation to aggressive lymphoma. If the FL cells lose this unique feature, they die, indicating that it is essential for FL survival.
Our investigation will use emerging technologies to describe the cellular interactions of FL cells expressing sIg-Mann with other cells in the microenvironment. We will then investigate the cellular consequences of this interaction and what happens if we block it with new therapeutic antibodies that we have generated in our laboratories. We will study the characteristics of this tumor-specific sugar using advanced techniques of glycobiology, and define the molecular features that can be used to predict its presence in diagnostic labs, helping refine diagnosis and prognosis of FL. We will perform experiments to verify that our new antibody is not unexpectedly toxic and is efficacious against tumor cells, before giving it to patients in a clinical trial.
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