IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines
Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.952231/full |
| _version_ | 1811267028512669696 |
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| author | Zhiliang Jia Dristhi Ragoonanan Kris Michael Mahadeo Jonathan Gill Richard Gorlick Elizabeth Shpal Shulin Li |
| author_facet | Zhiliang Jia Dristhi Ragoonanan Kris Michael Mahadeo Jonathan Gill Richard Gorlick Elizabeth Shpal Shulin Li |
| author_sort | Zhiliang Jia |
| collection | DOAJ |
| description | Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of IL-12 post administration. In this regard, we have developed a cell membrane-anchored and tumor-targeted IL-12-T (attIL12-T) cell product for avoiding toxicity from both IL-12 and T cells-induced cytokine release syndrome in peripheral tissues. A phase I trial using this product which seeks to avoid systemic toxicity and boost antitumor efficacy is on the horizon. Of note, this product also boosts the impact of CAR-T or TCR-T cell efficacy against solid tumors, providing an alternative approach to utilize CAR-T to overcome tumor resistance. |
| first_indexed | 2024-04-12T20:54:01Z |
| format | Article |
| id | doaj.art-d689a33e15a14aa58d32800f895edb1a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T20:54:01Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d689a33e15a14aa58d32800f895edb1a2022-12-22T03:17:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.952231952231IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokinesZhiliang Jia0Dristhi Ragoonanan1Kris Michael Mahadeo2Jonathan Gill3Richard Gorlick4Elizabeth Shpal5Shulin Li6Department of Pediatric Research, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pediatric Research, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pediatric Research, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pediatric Research, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pediatric Research, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pediatric Research, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesInterleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of IL-12 post administration. In this regard, we have developed a cell membrane-anchored and tumor-targeted IL-12-T (attIL12-T) cell product for avoiding toxicity from both IL-12 and T cells-induced cytokine release syndrome in peripheral tissues. A phase I trial using this product which seeks to avoid systemic toxicity and boost antitumor efficacy is on the horizon. Of note, this product also boosts the impact of CAR-T or TCR-T cell efficacy against solid tumors, providing an alternative approach to utilize CAR-T to overcome tumor resistance.https://www.frontiersin.org/articles/10.3389/fimmu.2022.952231/fullIL-12clinical trialCRScytokinesT cells |
| spellingShingle | Zhiliang Jia Dristhi Ragoonanan Kris Michael Mahadeo Jonathan Gill Richard Gorlick Elizabeth Shpal Shulin Li IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines Frontiers in Immunology IL-12 clinical trial CRS cytokines T cells |
| title | IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines |
| title_full | IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines |
| title_fullStr | IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines |
| title_full_unstemmed | IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines |
| title_short | IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines |
| title_sort | il12 immune therapy clinical trial review novel strategies for avoiding crs associated cytokines |
| topic | IL-12 clinical trial CRS cytokines T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.952231/full |
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