Katharina Maisel, PhD

Katharina Maisel, PhD

University of Maryland-College Park

Research Project:
Exploring Adjuvant Immunotherapy to Treat Lymphangioleiomyomatosis

Grant Awarded:

  • Innovation Award

Research Topics:

  • combination therapies experimental therapeutics
  • immunology immunotherapy

Research Disease:

  • LAM

Lymphangioleiomyomatosis (LAM) is a rare disease in which abnormal cells begin to grow out of control and eventually damage the lungs. LAM is usually diagnosed during reproductive years and often during or after pregnancy. The current treatment only stops progression of the disease and about 30% of patients with LAM do not respond to it. Therefore, new avenues for treating LAM are needed. Recent work, including our own, has shown that LAM has some similarities to cancer, including that LAM many suppress the immune response that would normally destroy any cancer-like cells. We found that using checkpoint inhibitors that have had significant success as cancer immunotherapies could improve survival in a mouse model of LAM. Based on this work, we have explored the use of another strategy for immune activation: adjuvants. These are materials often used in vaccine formulations and also explored as cancer immunotherapies, which stimulate immune cells to become activated. We have found that auxiliary CpG effectively improves survival in a mouse model of LAM. However, this survival is incomplete. We will investigate how CpG modulates the LAM immune response, and we will develop different strategies to overcome this. The findings will provide the foundation for translating this treatment to patients.

Update:

Our work will in year 1 of this proposal tested alternative dose regimens and combination therapies to enhance the effectiveness of immunotherapies in a model of LAM. We discovered that none of our hypothesized strategies enhanced treatment effectiveness. But in other studies we have found that instead combination with the standard of care, rapamycin, could enhance treatment outcomes. In year 2 we investigated why immunotherapy treatments called toll-like receptors (TLRs) still do not provide a cure. We have made significant progress testing different strategies to enhance TLR treatment outcomes in LAM. We found that timing of TLR treatments as well as alternating treatments did not significantly improve treatment outcomes in LAM. We will investigate mechanisms underlying the incomplete treatment efficacy in the next year.

Page last updated: September 17, 2024

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