Anti-tumor activity of a peptide combining patterns of insect alloferons and mammalian immunoglobulins in naïve and tumor antigen vaccinated mice

Abstract

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.