Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor
Natural compounds of various origins are intensively investigated for their antitumor activity. Potential benefits of antitumor therapy can be achieved when cytotoxic agents kill cancer cells and these dying cancer cells drive adoptive immunity to the tumor. This strategy was successfully demonstrat...
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/12/2804 |
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| author | Olga Troitskaya Mikhail Varlamov Anna Nushtaeva Vladimir Richter Olga Koval |
| author_facet | Olga Troitskaya Mikhail Varlamov Anna Nushtaeva Vladimir Richter Olga Koval |
| author_sort | Olga Troitskaya |
| collection | DOAJ |
| description | Natural compounds of various origins are intensively investigated for their antitumor activity. Potential benefits of antitumor therapy can be achieved when cytotoxic agents kill cancer cells and these dying cancer cells drive adoptive immunity to the tumor. This strategy was successfully demonstrated for chemotherapeutic drugs that induce immunogenic type of cell death (ICD) with release of DAMPs (danger associated molecular patterns) and exposure of “eat me” signals. In this study, we demonstrated that recombinant human milk peptide lactaptin (RL2) induces death of cancer cells with ICD hallmarks in vitro with the release of ATP and high-mobility group box 1 protein (HMGB1) and exposure of calreticulin and HSP70 on the external cell membrane. RL2-treated cancer cells were efficiently engulfed by phagocytic cells. Using the syngeneic mouse model, we demonstrated that RL2-treated MX-7 rhabdomyosarcoma cells confer long-term immune-mediated protection against challenge with live MX-7 cells. We also analyzed the combinatorial antitumor effect of vaccination with RL2-treated cells and the inhibition of indoleamine 2,3-dioxygenase (IDO) with ethyl pyruvate. Compared to solo anti-tumor immunization with RL2-treated cells, additional chemical inhibition of IDO demonstrated better long-term antitumor responses than vaccination alone. |
| first_indexed | 2024-03-10T19:06:08Z |
| format | Article |
| id | doaj.art-6e3e370ee3614b7fb116a9f32bf4a15d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:06:08Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6e3e370ee3614b7fb116a9f32bf4a15d2023-11-20T04:09:38ZengMDPI AGMolecules1420-30492020-06-012512280410.3390/molecules25122804Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO InhibitorOlga Troitskaya0Mikhail Varlamov1Anna Nushtaeva2Vladimir Richter3Olga Koval4Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, RussiaNatural compounds of various origins are intensively investigated for their antitumor activity. Potential benefits of antitumor therapy can be achieved when cytotoxic agents kill cancer cells and these dying cancer cells drive adoptive immunity to the tumor. This strategy was successfully demonstrated for chemotherapeutic drugs that induce immunogenic type of cell death (ICD) with release of DAMPs (danger associated molecular patterns) and exposure of “eat me” signals. In this study, we demonstrated that recombinant human milk peptide lactaptin (RL2) induces death of cancer cells with ICD hallmarks in vitro with the release of ATP and high-mobility group box 1 protein (HMGB1) and exposure of calreticulin and HSP70 on the external cell membrane. RL2-treated cancer cells were efficiently engulfed by phagocytic cells. Using the syngeneic mouse model, we demonstrated that RL2-treated MX-7 rhabdomyosarcoma cells confer long-term immune-mediated protection against challenge with live MX-7 cells. We also analyzed the combinatorial antitumor effect of vaccination with RL2-treated cells and the inhibition of indoleamine 2,3-dioxygenase (IDO) with ethyl pyruvate. Compared to solo anti-tumor immunization with RL2-treated cells, additional chemical inhibition of IDO demonstrated better long-term antitumor responses than vaccination alone.https://www.mdpi.com/1420-3049/25/12/2804milk peptidesrecombinant lactaptinimmunogenic cell deathantitumor vaccinationindoleamine 2,3-dioxygenase inhibitor |
| spellingShingle | Olga Troitskaya Mikhail Varlamov Anna Nushtaeva Vladimir Richter Olga Koval Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor Molecules milk peptides recombinant lactaptin immunogenic cell death antitumor vaccination indoleamine 2,3-dioxygenase inhibitor |
| title | Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor |
| title_full | Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor |
| title_fullStr | Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor |
| title_full_unstemmed | Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor |
| title_short | Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor |
| title_sort | recombinant lactaptin induces immunogenic cell death and creates an antitumor vaccination effect in vivo with enhancement by an ido inhibitor |
| topic | milk peptides recombinant lactaptin immunogenic cell death antitumor vaccination indoleamine 2,3-dioxygenase inhibitor |
| url | https://www.mdpi.com/1420-3049/25/12/2804 |
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