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A Safety and Feasibility Study of an Allogeneic Colon Cancer Cell Vaccine Administered with a Granulocyte–Macrophage Colony Stimulating Factor–Producing Bystander Cell Line in Patients with Metastatic Colorectal Cancer

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte–macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine.

Methods

A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer.

Results

A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies.

Conclusions

This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted.

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Acknowledgment

This work was supported by NIH K23 CA 104160-05 and NIH R01 CA112160 to R. S. L. Z. was supported by NIH K23 CA148964, a Johns Hopkins University School of Medicine Clinician Scientist Award, Lefkofsky Family Foundation, the NCI SPORE in Gastrointestinal Cancers P50 CA062924, and the Zhang Family Gift Fund/Susan Cohan Colon Cancer Foundation. E. M. J. was supported by the NCI SPORE in Gastrointestinal Cancers P50 CA062924.

Disclosure

Under a licensing agreement between Aduro Biotech and the Johns Hopkins University (JHU), the university and investigators are entitled to milestone payments and royalty on sales of the GM-CSF-secreting colon tumor vaccine product described herein.

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Authors and Affiliations

  1. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lei Zheng MD, PhD, Kevin C. Soares MD, Jennifer N. Uram PhD, Carol Judkins BS, Zhe Zhang MS, Beth Onners BS, Daniel Laheru MD, Drew Pardoll MD & Elizabeth M. Jaffee MD

  2. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lei Zheng MD, PhD & Kevin C. Soares MD

  3. The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lei Zheng MD, PhD, Kevin C. Soares MD, Jennifer N. Uram PhD, Carol Judkins BS, Beth Onners BS, Daniel Laheru MD & Elizabeth M. Jaffee MD

  4. The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lei Zheng MD, PhD, Kevin C. Soares MD, Daniel Laheru MD & Elizabeth M. Jaffee MD

  5. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lei Zheng MD, PhD, Kevin C. Soares MD, Jennifer N. Uram PhD, Carol Judkins BS, Zhe Zhang MS, Beth Onners BS, Daniel Laheru MD, Drew Pardoll MD & Elizabeth M. Jaffee MD

  6. Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA

    Barish H. Edil MD & Richard D. Schulick MD, MBA

  7. George Washington University, Washington, DC, USA

    Khaled El-Shami MD, PhD

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  1. Lei Zheng MD, PhD
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  2. Barish H. Edil MD
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  3. Kevin C. Soares MD
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  4. Khaled El-Shami MD, PhD
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  5. Jennifer N. Uram PhD
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  6. Carol Judkins BS
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  7. Zhe Zhang MS
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  8. Beth Onners BS
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  9. Daniel Laheru MD
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  11. Elizabeth M. Jaffee MD
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  12. Richard D. Schulick MD, MBA
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Corresponding author

Correspondence to Richard D. Schulick MD, MBA.

Additional information

Lei Zheng and Barish H. Edil contributed equally to this article, and both should be considered first author.

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Zheng, L., Edil, B.H., Soares, K.C. et al. A Safety and Feasibility Study of an Allogeneic Colon Cancer Cell Vaccine Administered with a Granulocyte–Macrophage Colony Stimulating Factor–Producing Bystander Cell Line in Patients with Metastatic Colorectal Cancer. Ann Surg Oncol 21, 3931–3937 (2014). https://doi.org/10.1245/s10434-014-3844-x

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  • DOI: https://doi.org/10.1245/s10434-014-3844-x

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