alloferon and Neoplasms

Alloferons are a group of naturally occurring peptides primarily isolated from insects and capable of stimulating mouse and human NK cell cytotoxicity towards cancer cells. In this paper we examined anti-tumor activity of alloferon-1 and its novel structural analog referred to as allostatine. The activity was tested in naïve and preventively tumor antigen vaccinated DBA/2 mice subcutaneously grafted with syngenic P388D1 mouse leukemia cells. In naïve animals allostatine demonstrated tumoristatic activity prevailing over alloferon-1 effect. The preventive vaccination caused only weak tumoristatic effect in 27% of vaccinated animals. The vaccination efficacy was dramatically enhanced by allostatine but not alloferon-1 administration: 65% of allostatine treated animals benefitted from tumoristatic effect and 30% was completely cured so that total number of positive responders grew to 95%. Thus, alloferon-1 and especially allostatine are worthy of further consideration as potential anti-cancer drugs. Allostatine seems to be particularly perspective for adjuvant cancer immunotherapy. Sequence similarity search revealed evolutionary conserved allostatine-like pattern inserted to CDR3 region of human and mouse immunoglobulins. By analogy with allostatine, the pattern may execute some unknown so far function in anti-tumor immune response regulation.

Topics: Amino Acid Sequence; Animals; Antigens, Neoplasm; Antineoplastic Agents; Cancer Vaccines; Cell Line, Tumor; Female; Humans; Immunoglobulins; Immunotherapy; Insecta; Mice; Mice, Inbred DBA; Neoplasms; Peptides; Sequence Alignment; Tumor Burden

Alloferons are a group of antiviral and anti-tumor peptides primarily isolated from insects and stimulating cytotoxic activity of natural killer cells in mammals including mice and humans. Alloferon-1 is currently used in the treatment of persistent viral infections; however its anti-tumor potential needs further preclinical assessment. Here we evaluate alloferon-1 anti-tumor activity in DBA/2 mice grafted with syngenic P388 murine leukemia cells. Alloferon-1 was applied alone or in combination with conventional cytotoxic chemotherapy (a mixture of cyclophosphamide, doxorubicin and vincristine). Alloferon-1 monotherapy demonstrated moderate tumoristatic and tumoricidal activities comparable with low dose chemotherapy. When alloferon-1 and the cytotoxic drugs were combined in a regime of pulse immunochemotherapy the combination anti-tumor activity evidently exceeded that of the treatments applied individually.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Models, Animal; Immunologic Factors; Mice; Mice, Inbred DBA; Neoplasm Transplantation; Neoplasms; Peptides; Tumor Burden