TY - JOUR

T1 - Immunogenicity of recombinant analog of antitumor protein lactaptin

AU - Tkachenko, A. V.

AU - Troitskaya, O. S.

AU - Semenov, D. V.

AU - Dmitrienko, E. V.

AU - Kuligina, E. V.

AU - Richter, V. A.

AU - Koval, O. A.

PY - 2017/11/9

Y1 - 2017/11/9

N2 - Therapeutic monoclonal antibodies and recombinant proteins including cytokines are commonly used in the treatment of cancer and inflammatory diseases. In most cases, these protein-based drugs exhibit a high therapeutic efficacy, which is unfortunately frequently associated with a variety of side effects. We have investigated the in vitro and in vivo immunogenicity of recombinant antitumor protein lactaptin (RL2). Based on the qRT-PCR analysis, we have shown that, in MDA-MB-231 human breast adenocarcinoma cells, RL2 suppresses the NF-kB signaling cascade that regulates the reactions of innate immunity. RL2 inhibits the expression of the CXCL1 protein and apoptosis inhibitor A20 and enhances expression of IkB, NF-kB repressor. The ELISA method has been used to evaluate the antibody titer in the blood of mice, which received single and triple intravenous or intraperitoneal injections of RL2. The multiplex immunoassay of 23 cytokines in the mice blood has shown that the RL2 injections lead to a slight increase in the levels of systemic pro-inflammatory cytokine interleukin-5 (IL-5) and keratinocyte chemoattractant (KC), a homologue of human macrophage inflammatory protein-1 (MIP-1). These observations indicate the low immunogenicity of the recombinant lactaptin analog, which can be considered to be a potential molecular drug candidate for further clinical development.

AB - Therapeutic monoclonal antibodies and recombinant proteins including cytokines are commonly used in the treatment of cancer and inflammatory diseases. In most cases, these protein-based drugs exhibit a high therapeutic efficacy, which is unfortunately frequently associated with a variety of side effects. We have investigated the in vitro and in vivo immunogenicity of recombinant antitumor protein lactaptin (RL2). Based on the qRT-PCR analysis, we have shown that, in MDA-MB-231 human breast adenocarcinoma cells, RL2 suppresses the NF-kB signaling cascade that regulates the reactions of innate immunity. RL2 inhibits the expression of the CXCL1 protein and apoptosis inhibitor A20 and enhances expression of IkB, NF-kB repressor. The ELISA method has been used to evaluate the antibody titer in the blood of mice, which received single and triple intravenous or intraperitoneal injections of RL2. The multiplex immunoassay of 23 cytokines in the mice blood has shown that the RL2 injections lead to a slight increase in the levels of systemic pro-inflammatory cytokine interleukin-5 (IL-5) and keratinocyte chemoattractant (KC), a homologue of human macrophage inflammatory protein-1 (MIP-1). These observations indicate the low immunogenicity of the recombinant lactaptin analog, which can be considered to be a potential molecular drug candidate for further clinical development.

KW - cytokines

KW - immune response

KW - Lactaptin

KW - multiplex analysis

KW - neutralizing antibody

KW - NF-kB

KW - therapeutic proteins

KW - Adenocarcinoma/drug therapy

KW - Antineoplastic Agents/immunology

KW - Breast Neoplasms/drug therapy

KW - Caseins/genetics

KW - Cytokines/immunology

KW - Humans

KW - MCF-7 Cells

KW - Recombinant Proteins/genetics

KW - Xenograft Model Antitumor Assays

UR - http://www.scopus.com/inward/record.url?scp=85049111445&partnerID=8YFLogxK

U2 - 10.7868/S0026898417050056

DO - 10.7868/S0026898417050056

M3 - Article

C2 - 29116065

AN - SCOPUS:85049111445

VL - 51

SP - 787

EP - 796

JO - Molekulyarnaya Biologiya

JF - Molekulyarnaya Biologiya

SN - 0026-8984

IS - 5

ER -