Immune to Cancer: The CRI Blog




Dr. Ellen Puré Answers Questions About The Basics of Immunotherapy After the 2021 CRI Virtual Immunotherapy Patient Summit

At the CRI Virtual Immunotherapy Patient Summit in October, patients and caregivers were eager to further their understanding of immunotherapy.

Ellen Puré, PhD, Grace Lansing Lambert Professor of Biomedical Science and chair of the department of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine, led the Immunotherapy 101 session.

We followed up with Dr. Puré after the event to discuss several more questions from attendees.

What other pathways are being used with the up-and-coming Immunotherapies other than the PD-L1 pathway?

There are two major categories of up-and-coming immunotherapies.  Those that, like anti-PD-1/PD-L1, are designed to take the brakes of the adaptive immune response (i.e. so-called checkpoint inhibitors or blockade), and those that are designed to directly enhance the adaptive immune response.  Examples of the former include targets such as CTLA-4 already in the clinic and in the pipeline are TIM3/Galectin-9, Vista, Lag-3. The latter include targets such as CD40/CD40L, OX40/OX40L, ICOS/ICOSL, GITR/GITRL, and 4-1BB/4-1BBL. 

Multiple innate immune cell pathways are also being targeted – some to enhance anti-tumor immunity and others to reverse the immunosuppressive environment in tumors.

I am a 51-year-old woman with an autoimmune disease. Can I still receive immunotherapy?

Due to the incidence of autoimmune-related adverse events, patients with preexisting active autoimmune diseases have largely been excluded from immunotherapy clinical trials. Moreover, some drugs, especially non-selective immunosuppressants, used to treat an autoimmune disease can negatively impact the efficacy of Immune Checkpoint Inhibitors (ICI).

That being said, however, there is evidence indicating that immune-checkpoint inhibitors (ICIs) may in some cases be safe and effective in patients with certain autoimmune diseases and that some more selective immunosuppressant drugs that are used to treat autoimmune diseases may not preclude the efficacy of ICIs.

Therefore, it is worth exploring the suitability of immunotherapy in the context of your specific situation with your oncologist keeping in mind that specific protocols for treating patients with an autoimmune disease with ICIs have not yet been standardized and might require individualized treatment plans.

What about immunotherapy for rare cancers – is there research being done for patients with sarcoma? 

There are increasing numbers of clinical trials of immunotherapy being conducted in patients with rare cancers including sarcomas, which are rare in adults but more prevalent in children.  In fact, there are immunotherapies already approved for use in sarcoma and many more being investigated.

Why does immunotherapy seem more effective for cancers that are more mutated?

Although not universally true, a higher mutation burden can be predictive or more favorable responses to immunotherapy.  Our immune systems are trained or educated to not destroy what is perceived as self but instead only to be activated by “non-self” or foreign cells or molecules.

Cancer cells are derived from our normal cells and therefore can lie under the radar of our immune systems.  The more mutations, the more different the cancer cell appears compared to the normal cells from which it was derived, and therefore making it more readily recognized as a foe by the immune system which it can therefore more readily alert and activate.  In addition, the immune response to each difference imposed by individual mutations can lead to the activation of different subpopulations of immune cells that can act collectively to generate an additive or synergistic immune response against tumor cells.

If cancer is in remission can we treat it with immunotherapy? 

A goal of immunotherapy is to tip the balance in favor of an effective immune response that the immune system can then maintain either by prolonged treatment in patients in remission or by cessation of treatment when a patient goes into “remission” – i.e. the cancer is in check – but treating again if or when the patient relapses.

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