Imiquimod enhances anti-lymphoma response in a tumor cell lysate vaccine and inhibits tumor cells growth.
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1
National Research Council Of Argentina, Argentina
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2
Instituto Nacional de Tecnología Agropecuaria (INTA), Argentina
Our aim was to study the immunomodulating and proapoptotic properties of the TLR7 agonist Imiquimod to be used as adjuvant in a tumor vaccine. Imiquimod showed an antiproliferative effect on LBC T-cell lymphoma in vitro at 48 and 72 h with doses between 0.5 and 200 μg/ml, inducing apoptosis in a dose dependent manner. BALB/c mice inoculated intraperitoneally twice with LBC cells lysates with or without 100 μg/mouse of Imiquimod and challenged one week later with LBC cells intraperitoneally, showed a significant increase in survival compared to un-immunized controls (LBC-lysate<0.05, LBC-lysate + IMQ<0.0005) and to mice receiving Imiquimod (p<0.0002; Logrank).Tumor incidence was only 5±5% in LBC-lysate+IMQ group whereas in LBC-lysate group was 52.5±2.5%. Although the percentages of specific cytotoxicity were above normal in both immunized groups (p<0.05, ANOVA), LBC-lysate+IMQ immunization induced the highest levels. A significant enhance in peritoneal cavity CD8+, CD4+ T and B cells (p<0.0001, ANOVA) with an increase IFNγ in supernatant from peritoneal cavity cells and splenocytes was demonstrated in all vaccinated groups compared to normal (p<0.001, ANOVA). Our vaccine also generated circulating antibodies in all immunized mice that rejected the tumor up to 75 days after challenge. Finally, mice that rejected the first tumor challenge were re-challenged with LBC tumor with an increased in survival in all immunized groups over the control (p<0.01, Logrank) with rejection rates close to 100%. We demonstrated that Imiquimod not only modulates immune response efficiently to reject tumor generating a long-lasting memory, but also is capable of inducing tumor apoptosis.
Keywords:
imiquimod,
T-cell lymphoma,
TLR7 agonist,
Apoptosis,
tumor cell lysate vaccine
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Mongini
C,
De Toro
J,
Hershlik
L,
Gravisaco
MJ,
Waldner
C and
Di Sciullo
P
(2013). Imiquimod enhances anti-lymphoma response in a tumor cell lysate vaccine and inhibits tumor cells growth..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01162
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Received:
31 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Claudia Mongini, National Research Council Of Argentina, Buenos Aires, Buenos Aires, 1121, Argentina, cmongini@icloud.com