Hematological Effects, Serum, and Pulmonary Cytokine Profiles in a Melanoma Mouse Model Treated with GK1

Abstract

Our results suggest that an intratumoral increase of cytokines with antitumor activity along with an intratumoral decrease of cytokines with protumor activity could explain, in part, the anti-melanoma effects of GK1 in a lung metastatic melanoma mouse model. Further studies must be performed to elucidate the precise mechanisms of action for GK1 peptide against melanoma, and their eventual application in humans.

Understanding the Anti-Tumor Properties Mediated by the Synthetic Peptide GK-1

“…Neutrophilia inside pulmonary blood vessels was also observed, without evidence of macroscopic or microscopic metastasis. In a melanoma lung metastatic model, GK-1 decreased lymphocyte count, while increased the number of neutrophils and decreased the serum levels of IFN-γ; on the other hand, an increase in the levels of IFN-γ and IL-12 in the intratumor (lung metastases) environment, along with a decrease in IL-17, IL-4, IL-22, and IL-23 was also observed [75,76]. The antitumor activities of IL-12 have been established in preclinical studies against various tumor cell lines; the increased concentration of the antitumor cytokine IL-12 found in primary tumors may enhance the damage to tumor cells, limiting the number of cancer cells detaching from the primary tumor [77][78][79].…”

Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy

“…The promising results from clinical trials recently led to the approval by the FDA of sipuleucel-T, a dendritic cell vaccine, for the treatment of stage IV metastatic but asymptomatic castrate-resistant prostate, the first therapeutic cancer vaccine [111]. Based on their format/content, they may be classified into several major categories, which include cell vaccines (tumor or immune cell), protein/peptide vaccines, and genetic (DNA, RNA and viral) vaccines [112].…”

“…These tumor cells are typically irradiated, combined with an immunostimulatory adjuvant (e.g., BCG), and then administered to the individual from whom the tumor cells were isolated; one major advantage of whole tumor cell vaccines is its potential to present the entire spectrum of tumorassociated antigens to the patient's immune system [114]. However, preparation of autologous tumor cell vaccines requires sufficient tumor specimen, which limits this technology to only certain tumor types or stages [112,114].…”

“…Allogeneic whole tumor cell vaccines typically contain two or three established human tumor cell lines, may be used to overcome many limitations of autologous tumor cell vaccines [115]. These include limitless sources of tumor antigens, standardized and large-scale vaccine production, reliable analysis of clinical outcomes, easy manipulation for expression of immunostimulatory molecules and costeffectiveness [112]. However, two multi-institutional randomized phase III trials in patients with stage III and IV melanoma failed to achieve a determination of vaccine efficacy, and therefore, these trials were discontinued [116].…”

“…The availability of patient's samples or specimens and the complex procedure of preparing individualized vaccines greatly limit the broad use of autologous cancer vaccines, including whole tumor cells or DCs [112]. Recombinant vaccines, which are based on peptides from defined tumor-associated antigens, and usually administered together with an adjuvant or an immune modulator, clearly have advantages.…”