CRI Funded Scientists

Craig L. Slingluff Jr., MD, Clinical Accelerator, Wade F. B. Thompson CLIP Investigator

University of Virginia Health System

Area of Research: All Cancers

Dr. Craig L. Slingluff Jr. serves as the vice-chair for research in the Department of Surgery at UVA Health, director of the UVA Cancer Center Human mmune Therapy Center, co-chair of the Melanoma Committee of ECOG, and a surgical oncologist. He is currently one of the two study chairs of the clinical trial “A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers” (NCT02643303).

This study examines combinations of two checkpoint immunotherapies, plus an immune-stimulating adjuvant, in a wide variety of patients diagnosed with breast cancersarcomahead and neck cancerlymphomamelanomabladder cancerkidney cancerprostate cancer, among other types of cancer. One checkpoint inhibitor, durvalumab (Imfinzi™), blocks the PD-L1 pathway, whereas the other, tremelimumab, blocks the CTLA-4 pathway. The adjuvant, poly ICLC, promotes an immune system response similar to that of vaccines.

Additional investigators working on this trial include:

  • Danae Hamouda, MD, Toledo University
  • Elizabeth Gaughan, MD, University of Virginia Health
  • Igor Puzanov, MD, Roswell Park Cancer Institute
  • Keisuke Shirai MD, Dartmouth University
  • Megan Kruse, MD, Cleveland Clinic
  • Michael Lowe, MD, Emory University
  • Nina Bhardwaj, MD, PhD, Icahn School of Medicine at Mount Sinai (Other study chair)

Dr. Slingluff is also a Wade F. B. Thompson CLIP Investigator. Therapeutic cancer vaccines are an emerging and promising immunotherapy approach. In addition to the information that tells the immune system what a patient’s tumor “looks like,” another important component of vaccines is the vaccine adjuvant, which help stimulate the immune system to act on that information. However, it remains unclear how exactly adjuvants work in the context of cancer vaccines, so Dr. Slingluff is investigating different adjuvants to define their mechanisms and effectiveness.

Specifically, he is examining vaccine-site samples from almost one hundred patients who received vaccines with either an IFA adjuvant, a poly ICLC adjuvant, or a combination of both. Through comprehensive analysis of these samples, Slingluff aims to:

  1. determine how these vaccine adjuvants support the activation of dendritic cells, a type of immune cell that orchestrates immune responses
  2. evaluate whether repeated same-site vaccination induces favorable activity with respect to T cells and immune cells known as myeloid cells
  3. assess how bacteria residing on the skin influence immune responses to vaccination 

Overall, the insights uncovered by these investigations should improve our understanding of cancer vaccine strategies and pave the way for the development of improved approaches for patients in the clinic.

Projects and Grants

A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers (NCT02643303)

University of Virginia Health System | Bladder Cancer, Breast Cancer, Head and Neck Cancer, Kidney Cancer, Lymphoma, Melanoma, Other Cancer, Prostate Cancer, Sarcoma, Skin Cancer | 2015

Effects of vaccine adjuvants and skin microbiome in the vaccine-site microenvironment

University of Virginia Health System | All Cancers | 2020

Barrier Molecules and Their Impact on T cell Infiltration in Melanoma

University of Virginia Health System | Melanoma | 2017

Retention integrins: induction and function on cancer-reactive T lymphocytes

University of Virginia Health System | Lung Cancer, Melanoma | 2015

Immunotherapeutic targeting cell surface neoantigen SAS1B

University of Virginia Health System | Kidney Cancer, Pancreatic Cancer | 2015

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