title: 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.
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.
authors.affiliation: German Cancer Research Center, Division of Translational Immunology; Department of Surgical Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Schirrmacher
authors.affiliation: German Cancer Research Center, Division of Translational Immunology; Department of Surgical Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schlude
authors.affiliation: German Cancer Research Center, Division of Translational Immunology; Department of Surgical Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.affiliation: German Cancer Research Center, Division of Translational Immunology; Department of Surgical Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D016466:CHO Cells; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
chemical_list: C000600160:ATV-NDV-bsHN-CD28 vaccine; D000951:Antigens, Neoplasm; D018106:CD28 Antigens; D019496:Cancer Vaccines