Christian S. Hinrichs, M.D.
Christian S. Hinrichs, M.D.
Assistant Clinical Investigator

Center for Cancer Research
National Cancer Institute

Building 10 - CRC, Room 3-3888
Bethesda, MD 20814
301-435-3027

Dr. Hinrichs studies immunotherapy for HPV+ cancers, which include cervical, oropharyngeal, anal, vulvar, vaginal, and penile malignancies. He has discovered personalized cellular and gene therapies for HPV+ cancers and is conducting clinical trials of these treatments. His laboratory is studying why these treatments work in some patients and not in others and is using what is learned to innovate more effective cancer treatments.

Areas of Expertise
1) immunotherapy, 2) human papillomavirus, 3) vaccines, 4) cervical cancer, 5) oropharyngeal cancer, 6) anal cancer
Link to Clinicaltrials.gov Protocol ID Referral Phone

A Phase I/II Study of T Cell Receptor Gene Therapy Targeting HPV-16 E6 for HPV-Associated Cancers

NCI-15-C-0005 1-866-820-4505

Cellular Therapy for Cancer

T-cell therapy can eradicate certain advanced malignancies, including melanoma and some B-cell malignancies. Application of this treatment modality is expanding as a result of genetic engineering that permits transfer of tumor specificity to any T cell through genes encoding tumor-specific receptors (T-cell receptors (TCR) or chimeric antigen receptors (CAR)). These genetically modified T cells can recognize tumors and mediate cancer regression in patients. Targeting of shared tumor/self antigens with this strategy can induce tumor responses but has been limited by autoimmune toxicities. We are working to apply cellular therapies to cancers that express antigens that are expressed by tumors but not by healthy tissues. Human papillomavirus (HPV)-associated cancers--virally induced malignancies that constitutively express foreign oncoproteins--are prototypical of these cancers and the focus of our efforts.

HPV-Associated Cancers

HPV-associated cancers occur at varied sites including the uterine cervix, oropharynx, anus, vagina, vulva, and penis. Metastatic disease from these malignancies is incurable, and durable palliation is rarely achieved with systemic therapies. Novel approaches for treating HPV-associated cancers are needed.

Research Strategy

HPV-associated cancers are attractive targets for T-cell-based therapies due to their expression of the E6 and E7 oncoproteins. These viral antigens are expressed by cancers but not by healthy tissues, and they contribute to the proliferation and survival of cancer cells. Thus, they are ideal therapeutic targets--tumor specific and functionally important. We are pursuing two T-cell-based approaches to targeting these antigens. The first is adoptive cell transfer therapy with tumor-infiltrating lymphocytes (TIL). TIL therapy involves the surgical resection of a patient's tumor, followed by the expansion of the T cells from the tumor to massive numbers, and then the reinfusion of the T cells back into the patient. This approach has resulted in complete and durable responses in metastatic melanoma. TIL can be generated from HPV-associated cancers and these TIL can have reactivity against the HPV E6 and E7 oncoproteins. A clinical trial (A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin for HPV-Associated Cancers) is presently underway to test the efficacy of TIL therapy for metastatic HPV-associated cancers. The second T-cell-based approach that we are studying uses T-cell receptor (TCR) gene engineered T cells. This strategy exploits gene transfer technology to confer tumor reactivity to T cells from the peripheral blood of patients. We are isolating T cells that recognize the HPV oncoproteins and the genes for the TCRs that mediate this recognition from HPV-positive cancer TIL. With these genes we are engineering T cells to have reactivity against the HPV oncoproteins and HPV-positive tumors to create the next generation of cellular therapies.

Scientific Focus Areas:
Biomedical Engineering and Biophysics, Cancer Biology, Clinical Research, Immunology
Selected Recent Publications
  1. Complete regression of metastatic cervical cancer following treatment with HPV-targeted tumor-infiltrating T cells.
    Stevanović S, Draper LM, Langhan MM, Campbell RE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, Restifo NP, Rosenberg SA, Hinrichs CS
    J. Clin. Oncology. In press: 2015. [ Journal Article ]
  2. Tran E, Turcotte S, Gros A, Robbins, PF, Lu YC, Dudley ME, Wunderlich Jr, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA
    Science. 9: 641-645, 2014. [ Journal Article ]
  3. Hinrichs CS and Rosenberg SA
    Immunol. Rev.. 257: 56-71, 2014. [ Journal Article ]
  4. Hinrichs CS and Restifo NP
    Nat Biotechnol. 31: 999-1008, 2013. [ Journal Article ]
  5. Hinrichs CS, Borman ZA, Gattinoni L, Yu Z, Burns WR, Huang J, Klebanoff CA, Johnson LA, Kerkar SP, Yang, S, Muranski M, Palmer DC, Morgan RA, Robbins PF, Rosenberg SA, Restifo NP
    Blood. 117: 808-814, 2011. [ Journal Article ]

Dr. Hinrichs received his B.A. and M.D. degrees from the combined 6-year program at the University of Missouri - Kansas City (UMKC). He completed a residency in general surgery at UMKC followed by a fellowship in surgical oncology at Roswell Park Cancer Institute. He then came to the Surgery Branch at the National Cancer Institute (NCI) as a surgical oncology fellow and studied tumor immunology in the laboratory of Dr. Nicholas P. Restifo. Subsequently he completed an internal medicine residency at George Washington University and a medical oncology fellowship with the Medical Oncology Branch, CCR. Dr. Hinrichs conducts translational research and clinical trials to develop T-cell therapies for cancers caused by human papillomaviruses.

Name Position
Tracy Campbell Postbaccalaureate Fellow
Lindsey Draper B.S. Summer Student
Sanja Stevanovic Ph.D. Postdoctoral Fellow (Visiting)

Summary

Dr. Hinrichs studies immunotherapy for HPV+ cancers, which include cervical, oropharyngeal, anal, vulvar, vaginal, and penile malignancies. He has discovered personalized cellular and gene therapies for HPV+ cancers and is conducting clinical trials of these treatments. His laboratory is studying why these treatments work in some patients and not in others and is using what is learned to innovate more effective cancer treatments.

Areas of Expertise
1) immunotherapy, 2) human papillomavirus, 3) vaccines, 4) cervical cancer, 5) oropharyngeal cancer, 6) anal cancer

Clinical Trials

Link to Clinicaltrials.gov Protocol ID Referral Phone

A Phase I/II Study of T Cell Receptor Gene Therapy Targeting HPV-16 E6 for HPV-Associated Cancers

NCI-15-C-0005 1-866-820-4505

Research

Cellular Therapy for Cancer

T-cell therapy can eradicate certain advanced malignancies, including melanoma and some B-cell malignancies. Application of this treatment modality is expanding as a result of genetic engineering that permits transfer of tumor specificity to any T cell through genes encoding tumor-specific receptors (T-cell receptors (TCR) or chimeric antigen receptors (CAR)). These genetically modified T cells can recognize tumors and mediate cancer regression in patients. Targeting of shared tumor/self antigens with this strategy can induce tumor responses but has been limited by autoimmune toxicities. We are working to apply cellular therapies to cancers that express antigens that are expressed by tumors but not by healthy tissues. Human papillomavirus (HPV)-associated cancers--virally induced malignancies that constitutively express foreign oncoproteins--are prototypical of these cancers and the focus of our efforts.

HPV-Associated Cancers

HPV-associated cancers occur at varied sites including the uterine cervix, oropharynx, anus, vagina, vulva, and penis. Metastatic disease from these malignancies is incurable, and durable palliation is rarely achieved with systemic therapies. Novel approaches for treating HPV-associated cancers are needed.

Research Strategy

HPV-associated cancers are attractive targets for T-cell-based therapies due to their expression of the E6 and E7 oncoproteins. These viral antigens are expressed by cancers but not by healthy tissues, and they contribute to the proliferation and survival of cancer cells. Thus, they are ideal therapeutic targets--tumor specific and functionally important. We are pursuing two T-cell-based approaches to targeting these antigens. The first is adoptive cell transfer therapy with tumor-infiltrating lymphocytes (TIL). TIL therapy involves the surgical resection of a patient's tumor, followed by the expansion of the T cells from the tumor to massive numbers, and then the reinfusion of the T cells back into the patient. This approach has resulted in complete and durable responses in metastatic melanoma. TIL can be generated from HPV-associated cancers and these TIL can have reactivity against the HPV E6 and E7 oncoproteins. A clinical trial (A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin for HPV-Associated Cancers) is presently underway to test the efficacy of TIL therapy for metastatic HPV-associated cancers. The second T-cell-based approach that we are studying uses T-cell receptor (TCR) gene engineered T cells. This strategy exploits gene transfer technology to confer tumor reactivity to T cells from the peripheral blood of patients. We are isolating T cells that recognize the HPV oncoproteins and the genes for the TCRs that mediate this recognition from HPV-positive cancer TIL. With these genes we are engineering T cells to have reactivity against the HPV oncoproteins and HPV-positive tumors to create the next generation of cellular therapies.

Scientific Focus Areas:
Biomedical Engineering and Biophysics, Cancer Biology, Clinical Research, Immunology

Publications

Selected Recent Publications
  1. Complete regression of metastatic cervical cancer following treatment with HPV-targeted tumor-infiltrating T cells.
    Stevanović S, Draper LM, Langhan MM, Campbell RE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, Restifo NP, Rosenberg SA, Hinrichs CS
    J. Clin. Oncology. In press: 2015. [ Journal Article ]
  2. Tran E, Turcotte S, Gros A, Robbins, PF, Lu YC, Dudley ME, Wunderlich Jr, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA
    Science. 9: 641-645, 2014. [ Journal Article ]
  3. Hinrichs CS and Rosenberg SA
    Immunol. Rev.. 257: 56-71, 2014. [ Journal Article ]
  4. Hinrichs CS and Restifo NP
    Nat Biotechnol. 31: 999-1008, 2013. [ Journal Article ]
  5. Hinrichs CS, Borman ZA, Gattinoni L, Yu Z, Burns WR, Huang J, Klebanoff CA, Johnson LA, Kerkar SP, Yang, S, Muranski M, Palmer DC, Morgan RA, Robbins PF, Rosenberg SA, Restifo NP
    Blood. 117: 808-814, 2011. [ Journal Article ]

Biography

Dr. Hinrichs received his B.A. and M.D. degrees from the combined 6-year program at the University of Missouri - Kansas City (UMKC). He completed a residency in general surgery at UMKC followed by a fellowship in surgical oncology at Roswell Park Cancer Institute. He then came to the Surgery Branch at the National Cancer Institute (NCI) as a surgical oncology fellow and studied tumor immunology in the laboratory of Dr. Nicholas P. Restifo. Subsequently he completed an internal medicine residency at George Washington University and a medical oncology fellowship with the Medical Oncology Branch, CCR. Dr. Hinrichs conducts translational research and clinical trials to develop T-cell therapies for cancers caused by human papillomaviruses.

Team

Name Position
Tracy Campbell Postbaccalaureate Fellow
Lindsey Draper B.S. Summer Student
Sanja Stevanovic Ph.D. Postdoctoral Fellow (Visiting)