Stephen M. Gottschalk, MD

Assistant Professor Department of Pediatrics Section of Hematology-Oncology, Baylor College of Medicine

 

 

 

Contact Information:
smg@bcm.edu
832-824-4179

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Education:
M.D., Medical School, University of Göttingen, Germany
Research Fellowship in Cell Biology, Baylor College of Medicine, Houston, Texas
Pediatric Residency, Baylor College of Medicine, Houston, Texas
Postdoctoral Fellowship, Pediatric Hematology-Oncology, Texas Children's Cancer Center and Hematology Service, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas

Research Interests:
We are interested in the immunotherapy for malignancies. This therapeutic approach has the major advantage of offering specific killing of malignant cells with minimal side effects. Our research is focused on the adoptive immunotherapy with cytotoxic T-cells (CTL). We are targeting Epstein-Barr virus (EBV) associated malignancies and malignancies that express the human epidermal growth factor receptor 2 (HER2).

Immunotherapy for EBV-associated malignancies:
Nasopharyngeal carcinoma (NPC) and Hodgkin's disease are 2 malignancies which are associated with EBV. We have shown that administration of EBV-CTL to patients with advanced, EBV-positive NPC or Hodgkin's disease is feasible, safe and results in significant anti-tumor activity in patients with low disease burden. We are currently devising strategies to a) increase the anti-NPC activity of EBV-CTL and b) enhance their expansion after adoptive transfer.

Immunotherapy for HER2-positive malignancies:
HER2 is a validated target for cancer therapy; however, the majority of anti-HER2 targeted therapies are restricted to cancer cells that express HER2 at high levels. This excludes a large group of malignancies expressing HER2 at low levels, including several pediatric malignancies such as medulloblastoma. We have shown that T cells expressing a HER2-specific chimeric antigen receptor (CAR) can effectively inhibit the growth of tumor cells, that express HER2 at low levels, ex vivo and in vivo. We are currently investigating strategies how to genetically modify HER2-specific T cells to increase their anti-tumor activity.

Selected Publications:
Waheed A, Gottschalk S, Hille A, Krentler C, Pohlmann R, Braulke T, Hauser H, Geuze H, von Figura K. (1988). Human lysosomal acid phosphatase is transported as a transmembrane protein to lysosomes in transfected baby hamster kidney cells. EMBO J 7:2351-2358

Gottschalk S, Waheed A, Schmidt B, Laidler P, von Figura K. (1989). Sequential processing of lysosomal acid phosphatase by a cytoplasmic thiol proteinase and a lysosomal aspartyl proteinase. EMBO J 8:3215-3219

Gottschalk S, Cristiano RJ, Smith LC, Woo SLC. (1994). Folate receptor mediated DNA delivery into tumor cells: potosomal disruption results in enhanced gene expression. Gene Therapy 1:185-191

Gottschalk S, Sparrow JT, Hauer J, Leland FE, Woo SLC, Smith LC (1996). A novel DNA-peptide complex for efficient transfer and expression in mammalian cells. Gene Therapy 3:448-457

Gottschalk S, Ng CYC, Perez M, Smith C, Sample C, Brenner MK, Heslop HE, Rooney CM (2001). An Epstein-Barr virus mutant associated with fatal lymphoproliferative disease unresponsive to virus-specific T cell therapy. Blood 97(4):835-843

Gahn B, Siller-Lopez F, Pirooz AD, Yvon E, Gottschalk S, Longnecker R, Brenner MK, Heslop HE, Aguilar-Cordova E, Rooney Cm (2001). Adenoviral Gene transfer into Dendritic Cells efficiently amplifies the immune response to the LMP2a-antigen: a potential treatment strategy for Epstein-Barr Virus - positive Hodgkin’s Lymphoma. Int. J. Cancer 93, 706-713

Gottschalk S, Edwards OL, Huls MH, Goltsova T, Davis AR, Heslop HE, Rooney CM (2003) Generating CTL against the subdominant Epstein-Barr virus LMP1 antigen for the adoptive Immunotherapy of EBV-associated malignancies. Blood 101(5): 1905-1912

Bollard CM, Straathof K, Huls MH, Leen A, Lacuesta K, Davis A, Gottschalk S; Brenner MK, Heslop HE, Rooney CM (2004). The Generation and Characterization of LMP2-specific CTLs for Use as Adoptive Tranfer From Patients with relapsed EBV-positive Hodgkin Disease. J Immunotherapy 27(4): 317-327

Gottschalk S, Rooney CM, Heslop HE (2005). Post-Transplant Lymphoproliferative Disorders. Annu Rev Med 56:29-44  

Bollard CM, Gottschalk S, Huls MH, Molldrem J, Przepoirka D, Rooney CM, Heslop HE (2006). In vivo expansion of LMP1 and 2-specific T cells in a patient who received donor-derived EBV-specific T cells after allogenic stem cell transplantation. Leukemia & Lymphoma 47(5):837-842

Savoldo B, Goss JA, Hammer MM, Zhang L, Lopez T, Gee AP, Lin YF, Quiros-Tejeira RE, Reinke P, Schubert S, Gottschalk S, Finegold MJ, Brenner MK, Rooney CM, Heslop HE (2006). Treatmet of solid organ transplant recipients with autologous Epstein-Barr Virus-specific cytotoxic T lymphocytes (CTL). Blood 108(9):2942-9.

Leen A, Ratnayake M, Foster A, Heym K, Ahmed N, Rooney CM, Gottschalk S (2007). Contact activated Monocytes: efficient antigen presenting cells for the stimulation of antigen-specific T cells. J Immunother 30:96-107

Seiler MP, Gottschalk S, Cerullo V, Ratnayake M, Mane VP, Clarke C, Ng P, Palmer J, Rooney CM, Lee B (2007). Dendritic Cell function after gene transfer with adenovirus-calcium phosphate co-precipitates. Mol Ther 15(2):386-92

Ahmed A, Ratnayake M, Savoldo B, Perlaky L, Dotti G, Wels WS, Bhattacharjee MB, Gilbertson RJ, Shine HD, Weiss HL, Rooney CM, Heslop HE, Gottschalk S (2007) Regression of experimental medulloblastoma following transfer of HER2-specific T cells. Cancer Res (in press)

 

©2002, Cell And Gene Therapy, Baylor College of Medicine
One Baylor Plaza, N1002, Houston, TX 77030, (713)798-1246
URL: http://www.bcm.edu/genetherapy Email:cagt@bcm.edu
(Modified:August 15, 2006- SM)