Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study

  • Authors:
    • Volker Schirrmacher
    • Christoph Schlude
    • Jürgen Weitz
    • Philipp Beckhove
  • View Affiliations

  • Published online on: October 6, 2014     https://doi.org/10.3892/ijo.2014.2692
  • Pages: 71-77
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

T‑cell costimulation is necessary to induce a response of naïve T cells. Whether T‑cell costimulation can also cause reactivation of unreactive, possibly anergized memory T cells (MTCs) from late‑stage cancer patients is unknown. To investigate this question, we developed a bispecific anti‑CD28 fusion protein (bsHN‑CD28) which can easily be attached to the vaccine ATV‑NDV. This virus‑modified autologous tumor cell vaccine has already shown effectivity in colon cancer patients following resection of liver metastases. In this phase Ⅰ clinical study, 14 colorectal carcinoma (CRC) patients with late‑stage disease which could not be operated anymore with curative intent were treated with the vaccine ATV‑NDV to which bsHN‑CD28 was attached. No severe adverse events were recorded. All patients showed an immunological response of tumor‑reactive T cells, at least once during the course of five vaccinations. Also, we demonstrate a dose‑response relationship with the costimulatory molecule added to the vaccine. A partial response of metastases was documented in four patients. The study suggests that the three‑component vaccine is safe and can reactivate possibly anergized T cells from a chronic disease like advanced‑stage cancer.
View Figures
View References

Related Articles

Journal Cover

January 2015
Volume 46 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Schirrmacher, V., Schlude, C., Weitz, J., & Beckhove, P. (2015). Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study. International Journal of Oncology, 46, 71-77. https://doi.org/10.3892/ijo.2014.2692
MLA
Schirrmacher, V., Schlude, C., Weitz, J., Beckhove, P."Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study". International Journal of Oncology 46.1 (2015): 71-77.
Chicago
Schirrmacher, V., Schlude, C., Weitz, J., Beckhove, P."Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study". International Journal of Oncology 46, no. 1 (2015): 71-77. https://doi.org/10.3892/ijo.2014.2692