Immuno-Oncology Resource Center

Immuno-Oncology Resource Center

August 07, 2019
3 min read

Research initiative aims to better understand link between immunotherapy, type 1 diabetes

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Cheryl Selinsky
Cheryl Selinsky

The Parker Institute for Cancer Immunotherapy, in collaboration with the Juvenile Diabetes Research Foundation and Helmsley Charitable Trust, have formed a cancer and diabetes research initiative to better understand the association between immunotherapy treatment and subsequent risk for type 1 diabetes.

The three nonprofit organizations are jointly funding the initiative with $10 million during a 3-year period.

“The clinical success of immune checkpoint inhibitors has changed the face of cancer therapy, extending lives of patients who previously had few choices. In rare cases, these patients develop insulin-dependent diabetes, and nobody truly understands how or why,” Jeffrey Bluestone, PhD, A.W. and Mary Margaret Clausen distinguished professor of metabolism and endocrinology at University of California, San Francisco, and CEO of Parker Institute for Cancer Immunotherapy, said in a press release.

“In putting together this research initiative, we hope to answer key questions that will help us predict and prevent autoimmunity following immunotherapy treatment in the future,” Bluestone said. “This is of increasing importance as more patients are being treated with checkpoint inhibitors and other immunotherapies.”

HemOnc Today spoke with Cheryl Selinsky, PhD, vice president of research operations at Parker Institute for Cancer Immunotherapy, about the need for an initiative such as this and when she anticipates results from ongoing research will become available.

Question: Why is an initiative such as this needed ?

Answer: With immunotherapies being placed into different disease indications, we are beginning to see an increased incidence of adverse events. There is, of course, a balance between ramping up the immune system to a point where it can effectively deal with the cancer and then overshooting to the point where it starts recognizing normal tissue. We have seen really good cure rates in some cancers — such as melanoma — but we are beginning to see some of these patients coming in with autoimmune conditions, including type 1 diabetes. Incidence is relatively low — roughly 1% of patients experience these adverse events — but as we have more clinical trials of additional immunotherapies, we anticipate that the rate will increase. We hope to get ahead of these adverse events and find a way to predict who may be at risk for developing them before they go on treatment. In addition, we would like to understand the biology of what happens when they have these adverse events, the cause, and who may be better managed at the outset of any new therapy.


Q: How are you conducting the research ?

A: We first looked at anecdotal evidence from the sites we work with for clinical trials to get a sense of when these adverse events start to arise. We then brought together people who are particularly interested in type 1 diabetes, including representatives of the Juvenile Diabetes Research Foundation and Helmsley Charitable Trust, to start an initiative through which researchers and physicians seeing patients on the front line can design a study and collect samples from patients on immunotherapy. It is critical to start the collections before the patients start treatment. We are prospectively collecting longitudinal blood samples from 1,600 patients before immunotherapy, shortly after their second therapy dose, 6 months after the start of therapy and 12 months after therapy. We will gather plasma samples as close to any adverse event as possible and follow patients throughout the remainder of treatment. We will have a very rich set of samples with the appropriate clinical information to interpret what happens when they experience an adverse event.

Q: When do you anticipate initial results will be available?

A: I anticipate that we will see results on an ongoing basis, but because we are following patients longitudinally, we will have to wait until these patients experience an adverse event. Samples from patients who do not experience an adverse event are still useful. We will conduct a case-control comparison. In the meantime, we are looking at the genetics that may predispose an individual to these adverse events so we can start conducting genetic-based analyses and then, for the patients who experience adverse events, figure out if there is a correlate. We are lining up assays to interrogate these patients so that when they have an adverse event, we will be able to seize on that and start the research.

Q: What is your ultimate hope for the initiative?

A: The initiative will inform prediction and management in the context of immunotherapy, and also provide more insights into the biology of type 1 diabetes. We have a good feel for some of the genetic underpinnings, but probably not all of them. We ultimately want to find a way to better combine the drugs to keep this from happening.


Q: Is there anything else that you would like to mention?

A: This has been a great opportunity to engage with community-based cancer centers and the smaller practices that do not necessarily contribute to research studies. We have partnered with a group that has a network of community cancer centers and they are providing a large number of patients who are on standard-of-care checkpoint therapy, not involved in clinical trials and very motivated to participate in research. Additionally, although we started out looking at type 1 diabetes, there are other adverse events that happen in the context of immunotherapy. This will provide an infrastructure and basis for those other types of adverse events. – by Jennifer Southall

For more information:

Cheryl Selinsky, PhD, can be reached at Parker Institute for Cancer Immunotherapy, 1 Letterman Drive, Suite D3500, San Francisco, CA 94129.

Disclosure: Selinksy reports no relevant financial disclosures.