Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition
Holly A Maulhardt,1 Alyson M Marin,1 Gere S diZerega1,2 1US Biotest, Inc, San Luis Obispo, CA, USA; 2Nanology, LLC, Fort Worth, TX, USACorrespondence: Gere S diZerega, US Biotest, Inc, 231 Bonetti Drive, Suite 240, San Luis Obispo, CA, 93401, USA, Tel +01 805 595 1300, Email Gere.diZerega@usbiotest....
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2024-01-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/intratumoral-treatment-of-melanoma-tumors-with-large-surface-area-micr-peer-reviewed-fulltext-article-IJN |
| _version_ | 1827375941550080000 |
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| author | Maulhardt HA Marin AM diZerega GS |
| author_facet | Maulhardt HA Marin AM diZerega GS |
| author_sort | Maulhardt HA |
| collection | DOAJ |
| description | Holly A Maulhardt,1 Alyson M Marin,1 Gere S diZerega1,2 1US Biotest, Inc, San Luis Obispo, CA, USA; 2Nanology, LLC, Fort Worth, TX, USACorrespondence: Gere S diZerega, US Biotest, Inc, 231 Bonetti Drive, Suite 240, San Luis Obispo, CA, 93401, USA, Tel +01 805 595 1300, Email Gere.diZerega@usbiotest.comAbstract: The effects of intratumoral (IT) large surface area microparticle paclitaxel (LSAM-PTX) alone and in combination with systemic administration of the programmed cell death protein antibody (anti-mPD-1) were evaluated in a syngeneic murine model of melanoma. Groups of mice with subcutaneously implanted Clone M3 (Cloudman S91) tumors were treated with single and combination therapies. Tumor volume (TV) measurements, body weights, and clinical observations were followed in-life. At end of study, tumor-site tissues were collected, measured, and processed for flow cytometry along with blood and lymph nodes. The combination of LSAM-PTX + anti-mPD-1 resulted in an antitumoral response, which produced a significant decrease in TV compared to control animals. TV decreases also occurred in the LSAM-PTX and anti-mPD-1 groups. Flow cytometry analysis found increases in granulocytes and M2 macrophages and decreases in dendritic cells (DC) and monocytic myeloid-derived suppressor cells (M-MDSC) in tumor-site tissues. Increases in granulocytes and decreases in CD4+ T cells, macrophages, and M1 macrophages were found in the blood of animals administered the combination treatment. Increases in natural killer (NK) cells were found in lymph node tissue in the combination treatment group. These findings suggest that IT LSAM-PTX may provide benefit in the local treatment of melanomas and may synergize with systemic anti-PD-1 therapy, leading to additional tumoricidal outcomes without added systemic toxicity.Keywords: clone M-3, nanopac, combinatorial immunotherapy, PD-1 |
| first_indexed | 2024-03-08T12:01:38Z |
| format | Article |
| id | doaj.art-7590b93a0e674f5fb4e9cd3d2439937e |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-03-08T12:01:38Z |
| publishDate | 2024-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-7590b93a0e674f5fb4e9cd3d2439937e2024-01-23T18:27:27ZengDove Medical PressInternational Journal of Nanomedicine1178-20132024-01-01Volume 1968969789867Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint InhibitionMaulhardt HAMarin AMdiZerega GSHolly A Maulhardt,1 Alyson M Marin,1 Gere S diZerega1,2 1US Biotest, Inc, San Luis Obispo, CA, USA; 2Nanology, LLC, Fort Worth, TX, USACorrespondence: Gere S diZerega, US Biotest, Inc, 231 Bonetti Drive, Suite 240, San Luis Obispo, CA, 93401, USA, Tel +01 805 595 1300, Email Gere.diZerega@usbiotest.comAbstract: The effects of intratumoral (IT) large surface area microparticle paclitaxel (LSAM-PTX) alone and in combination with systemic administration of the programmed cell death protein antibody (anti-mPD-1) were evaluated in a syngeneic murine model of melanoma. Groups of mice with subcutaneously implanted Clone M3 (Cloudman S91) tumors were treated with single and combination therapies. Tumor volume (TV) measurements, body weights, and clinical observations were followed in-life. At end of study, tumor-site tissues were collected, measured, and processed for flow cytometry along with blood and lymph nodes. The combination of LSAM-PTX + anti-mPD-1 resulted in an antitumoral response, which produced a significant decrease in TV compared to control animals. TV decreases also occurred in the LSAM-PTX and anti-mPD-1 groups. Flow cytometry analysis found increases in granulocytes and M2 macrophages and decreases in dendritic cells (DC) and monocytic myeloid-derived suppressor cells (M-MDSC) in tumor-site tissues. Increases in granulocytes and decreases in CD4+ T cells, macrophages, and M1 macrophages were found in the blood of animals administered the combination treatment. Increases in natural killer (NK) cells were found in lymph node tissue in the combination treatment group. These findings suggest that IT LSAM-PTX may provide benefit in the local treatment of melanomas and may synergize with systemic anti-PD-1 therapy, leading to additional tumoricidal outcomes without added systemic toxicity.Keywords: clone M-3, nanopac, combinatorial immunotherapy, PD-1https://www.dovepress.com/intratumoral-treatment-of-melanoma-tumors-with-large-surface-area-micr-peer-reviewed-fulltext-article-IJNclone m-3nanopaccombinatorial immunotherapypd-1 |
| spellingShingle | Maulhardt HA Marin AM diZerega GS Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition International Journal of Nanomedicine clone m-3 nanopac combinatorial immunotherapy pd-1 |
| title | Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition |
| title_full | Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition |
| title_fullStr | Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition |
| title_full_unstemmed | Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition |
| title_short | Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition |
| title_sort | intratumoral treatment of melanoma tumors with large surface area microparticle paclitaxel and synergy with immune checkpoint inhibition |
| topic | clone m-3 nanopac combinatorial immunotherapy pd-1 |
| url | https://www.dovepress.com/intratumoral-treatment-of-melanoma-tumors-with-large-surface-area-micr-peer-reviewed-fulltext-article-IJN |
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