Michael S. Sabel, M.D.
Associate Professor of Surgery
The potential for the immune system to recognize and eradicate malignant disease has been well established, but the translation of immunotherapies from the bench to the bedside has been fraught with difficulties. A "catch-22" in the field of cancer vaccines is that the most immunogenic approaches are those that use the patient's own tumor to create the vaccine, but this is not only technically challenging and extremely expensive, it also greatly limits the number of patients who might benefit. To overcome this challenge, my lab has focused on "neoadjuvant immunotherapy," also known as "in situ vaccination," where we use the tumor as the base of the vaccine. In one approach, we use poly-lactic acid microspheres to slowly release pro-inflammatory cytokines within the tumor microenvironment to stimulate a systemic immune response. We have identified novel combinations of cytokines (interleukin-12 in combination with tumor-necrosis factor alpha or with interleukin-18) that are extremely effective and are working to define the mechanisms by which these cytokines work in concert. Our lab has also been a leader in examining the role that cryoablation (freezing tumors) plays in stimulating an anti-tumor immune response, and is currently investigating the potential of cryoablation followed by the intratumoral delivery of immature dendritic cells.
- Staren ED, Sabel MS, Gianakakis L, Weiner GD, Hart VM, Gorski M, Haklin M, Koukoulis G. Cryosurgery of Breast Carcinoma. Archives of Surgery 1997; 132:28-34.
- Conway TF, Sabel MS, Sugano M, Egilmez NK, Chen FA, Bankert RB. Growth of human tumor xenografts in SCID mice quantified using an immunoassay for tumor marker protein in serum. Journal of Immunological Methods 2000;233:57-65.
- Sabel MS, Yamada M, Egilmez NK, Chen FA, Bankert RB. CD40 expression on human lung cancer correlates with metastatic spread. Cancer Immunology, Immunotherapy 2000;49(2):101-8.
- Sabel MS, Conway TF, Chen FA, Bankert RB. Monoclonal antibodies directed against the T-cell activation molecule CD137 (ILA/4-1BB) block human lymphocyte mediated suppression of tumor xenografts in SCID mice. Journal of Immunotherapy 2000; 23(3): 362-368.
- Egilmez NK, Jong YS, Sabel MS, Jacob JS, Mathiowitz E, Bankert RB. In situ tumor vaccination with interleukin-12 encapsulated biodegradable microspheres: Induction of tumor regression and potent antitumor immunity. Cancer Res. 2000;60(14);3832-7.
- Sabel MS, Hill HC, Egilmez NK, Mathiowitz E, Yong YS, Bankert RB. Neoadjuvant therapy with IL-12 loaded microspheres reduces local recurrence and distant metastases. Surgery 2001;130(3):470-8.
- Sabel MS, Sondak VK. Tumor Vaccines: A Role in Preventing Recurrence? American Journal of Clinical Dermatology. 2002; 3(9): 609-616.
- Hill HC, Conway TF, Sabel MS, Jong YS, Mathiowitz E, Bankert RB, Egilmez NK. Tumor vaccination with Interleukin-12 and Granulocyte-Macrophage Colony-Stimulating Factor-Encapsulated Microspheres: Co-induction of Innate and Adaptive Anti-Tumor Immunity and Cure of Disseminated Disease. Cancer Research 2003; 62:7254-7263
- Sabel MS, Skitzki J, Stoolman L, Egilmez NK, Mathiowitz E, Bailey N, Chang W-J, Chang AE. Intratumoral IL-12 and TNF-alpha loaded microspheres leads to regression of breast cancer and systemic anti-tumor immunity. Annals of Surgical Oncology 2004 11: 147-156
- Sabel MS, Kaufman CS, Whitworth P, Chang H, Stocks LH, Simmons R, Schultz M. Cryoablation of early-stage breast cancer: Work-in-progress report of a multi-institutional trial. Annals of Surgical Oncology. 2004;11(5):542-549.
- Roubidoux MA, Sabel MS, Bailey JE, Kleer CK, Klein KA, Helvie KA. Mammographic and sonographic findings in ultrasound guided cryoablation of small breast cancers. Radiology. 2004;233:857-867.
- McLean M, Wallace HL, Sharma A, Hill HC, Sabel MS, Egilmez NK. A Balb/C murine lung alveolar carcinoma used to establish a surgical spontaneous metastasis model. Clinical and Experimental Metastases. 2004;21:363-369.
- Sabel MS, Nehs MA, Su G, Lowler K, Ferrara J, Chang AE. Immunological response to cryoablation of breast cancer. Breast Cancer Research and Treatment. 2005;90:97-104.
- Sabel MS, Hess SD, Egilmez NK, Conway TF, Chen, F-A, Bankert RB. CTLA-4 blockade augments human T lymphocyte-mediated suppression of lung tumor xenografts in SCID mice. Cancer Immunology and Immunotherapy. 2005;54:944-952.
- Sondak VK, Sabel MS, Mule' JJ. Allogeneic and autologous melanoma vaccines: Where have we been and where are we going? Clinical Cancer Research. 2006;12(7 Suppl):2337s-2341s.
- Arora A, Su G, Mathiowitz E, Chang AE, Sabel MS. Neoadjuvant intratumoral cytokine-loaded microspheres are superior to postoperative vaccines in generating systemic anti-tumor immunity. Journal of Surgical Oncology. 2006;94:403-412.
- Sabel MS, Arora A, Su G, Chang AE. Adoptive Immunotherapy of Breast Cancer with Lymph Node Cells Primed By Cryoablation of the Primary Tumor. Cryobiology. 2006;53:360-366.
- Sabel MS, Arora A, Su G, Mathiowitz E, Reineke JJ, ChangAE. Synergistic Effect of Intratumoral IL-12 and TNF- Microspheres: Systemic Anti-Tumor Immunity is Mediated by both CD8+ CTL and NK cells. Surgery. In Press.
- Sabel MS, Arora A, Su G, Mathiowitz E, Reineke JJ, Chang AE. Generation of a Tumor-Specific CD8+ T-cell Response After Intratumoral Injection of IL-12 and IL-18 Loaded Poly Lactic Acid Microspheres. Journal of Immunotherapy. In Press.
- Sabel MS, Edge SB. In situ ablation of breast cancer. Breast Disease 2001;12(1):131-140.
- Sabel MS, Sondak VK. Melanoma vaccines: Breakthrough or Bust? [Editorial] Cancer Investigation 2002;20:1114-1116.
- Sabel MS. In situ vaccination of cancer with cytokine loaded controlled-release biodegradable microspheres. Research Advances in Cancer 2003;3:199-205.
- Sabel MS, Nehs M. Immunologic Approaches to Breast Cancer Treatment. Surgical Oncology Clinics of North America. 2005;14(1):1-31.
- Tsai S, Sabel MS. Translational Research in Melanoma. Surgical Oncology Clinics of North America. In Press.
- Sabel MS. Cryoablation of breast cancer: No need to turn a cold shoulder. Journal of Surgical Oncology. In Press.