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.

Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

“…By manipulating costimulatory molecules to increase the number and activity of tumor antigen-specific T cells and inhibit tumor growth. The expression of T-cell costimulatory molecules in colon cancer was significantly higher than that in the control group (27). In the results of GSEA enrichment analysis, the items such as anti-processing and presentation, toll like receptor signaling pathway are related to the progress of colon cancer.…”

Fifty Years of Clinical Application of Newcastle Disease Virus: Time to Celebrate!

“…This was shown by breaking T-cell tolerance [68,69], and also by breaking resistance to immune checkpoint blockade immunotherapy [70]. …”

Application of Newcastle disease virus in the treatment of colorectal cancer

“…After using ATV-NDV-bsHN-CD28 to treat 14 cases of advanced CRC not surgically treatable in the phase I clinical trial, no tumor-reactive blood circulation MTCs were detected in any of the patients before vaccination; however, all patients exhibited the immune response of tumor-reactive MTCs at least once during five vaccinations. Among them, four patients experienced partial diminishment of metastases[83].…”