- Presentation of in vitro studies of RM-0256, a novel anti-PD-L1 antibody conjugated to IR700, which comprises a dual mode of photoimmunotherapy: depletion of PD-L1 expressing tumor cells and depletion of PD-L1 expressing immunosuppressive cells
- In vivo studies of the treatment resulted in more effective tumor growth suppression compared to anti-PD-L1 antibody alone in an anti-PD-L1 sensitive mouse tumor model and tumor growth suppression compared to saline in an anti-PD-L1 resistant mouse tumor model
- A GLP toxicity study suggested that RM-0256 will be clinically well-tolerated
SAN DIEGO, CA, USA I September 19, 2024 I Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting therapies based on its proprietary Alluminox™ platform, today announces that the research results of the preclinical studies for PD-L1-targeted photoimmunotherapy were presented at the 83rd Annual Meeting of the Japanese Cancer Association (JCA2024) in Fukuoka, Japan on September 20, 2024 (JST).
The key findings presented at JCA2024
Abstract Title: PD-L1 photoimmunotherapy kills immunosuppressive myeloid cells to activate local and systemic antitumor immunity
Presenter: Amy H. Thorne, Ph.D. (Rakuten Medical, Inc.)
Abstract Number: 30050
- It has been observed in in vitro studies that this photoimmunotherapy has a dual mechanism of action (MoA): depletion of PD-L1 expressing tumor cells and depletion of PD-L1 expressing immunosuppressive cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). In addition to this dual MoA, the potential for systemic immune checkpoint inhibition was also observed.
- It has been observed in in vivo studies that the treatment resulted in more effective tumor growth suppression compared to anti-PD-L1 antibody alone in an anti-PD-L1 sensitive mouse tumor model and tumor growth suppression compared to saline control in an anti-PD-L1 resistant mouse tumor model.
- It has been observed in in vivo studies that the treatment affects the tumor microenvironment balance by depleting immunosuppressive tumor microenvironment cells and maintains checkpoint inhibition to enhance CD8+ T cell activation.
- RM-0256 was well-tolerated in a GLP toxicity study in which the drug was administered repeatedly to cynomolgus monkeys.
Based on the preclinical study data, Rakuten Medical is currently considering new clinical development opportunities.
About RM-0256
RM-0256 is a conjugate of a newly developed anti-PD-L1 antibody and IRDye®700DX (IR700), a light-activatable dye, that accumulates specifically on PD-L1-expressing cells. PD-L1 is a protein that inhibits the anti-cancer immune response by deactivating killer T cells, via binding to PD-1 which is abundantly expressed on the T cell surface1. PD-L1 is expressed in many solid tumors such as melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck, among others, helping these tumors evade the immune system2. In addition to being present on tumor cells, PD-L1 is also expressed on suppressive immune cells within the tumor microenvironment such as tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs)3. In preclinical studies, PD-L1-targeted photoimmunotherapy resulted in the necrosis of PD-L1 expressing target cells and activation of an anti-cancer immune response. Furthermore, RM-0256 was shown to inhibit the PD-L1:PD-1 interaction, and thus is expected to act systemically as an immune checkpoint inhibitor, further enhancing the anticancer immune response after PD-L1-targeted photoimmunotherapy.
About Rakuten Medical, Inc.
Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing and tumor necrosis. Alluminox therapies have not yet been approved outside of Japan. Rakuten Medical is committed to its mission to conquer cancer by delivering its innovative treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 5 countries/regions, including the United States, where it is headquartered, Japan, Taiwan, Switzerland and India. For more information, visit https://rakuten-med.com/us/
About Alluminox™ platform
The Alluminox™ platform is an investigational technology platform based on a cancer therapy called photoimmunotherapy, which was developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Rakuten Medical is developing the Alluminox platform as a technology consisting of a drug, device, and other related components. The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding. The device component consists of a light source that locally illuminates the targeted cells with light to transiently activate the drug. Pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cancer cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Outside of Japan, Alluminox therapies have not yet been approved by any regulatory authority.
References
1. Chunwan Lu, Priscilla S. Redd, Jeffrey R. Lee, Natasha Savage & Kebin Liu (2016) The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells, OncoImmunology, 5:12, DOI: 10.1080/2162402X.2016.1247135
2. Kythreotou A, Siddique A, Mauri FA, et al. PD-L1Journal of Clinical Pathology 2018;71:189-194. https://jcp.bmj.com/content/71/3/189
3. Shklovskaya, E.; Rizos, H. Spatial and Temporal Changes in PD-L1 Expression in Cancer: The Role of Genetic Drivers, Tumor Microenvironment and Resistance to Therapy. Int. J. Mol. Sci. 2020, 21, 7139. https://doi.org/10.3390/ijms21197139
SOURCE: Rakuten Medical
Post Views: 2,513
- Presentation of in vitro studies of RM-0256, a novel anti-PD-L1 antibody conjugated to IR700, which comprises a dual mode of photoimmunotherapy: depletion of PD-L1 expressing tumor cells and depletion of PD-L1 expressing immunosuppressive cells
- In vivo studies of the treatment resulted in more effective tumor growth suppression compared to anti-PD-L1 antibody alone in an anti-PD-L1 sensitive mouse tumor model and tumor growth suppression compared to saline in an anti-PD-L1 resistant mouse tumor model
- A GLP toxicity study suggested that RM-0256 will be clinically well-tolerated
SAN DIEGO, CA, USA I September 19, 2024 I Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting therapies based on its proprietary Alluminox™ platform, today announces that the research results of the preclinical studies for PD-L1-targeted photoimmunotherapy were presented at the 83rd Annual Meeting of the Japanese Cancer Association (JCA2024) in Fukuoka, Japan on September 20, 2024 (JST).
The key findings presented at JCA2024
Abstract Title: PD-L1 photoimmunotherapy kills immunosuppressive myeloid cells to activate local and systemic antitumor immunity
Presenter: Amy H. Thorne, Ph.D. (Rakuten Medical, Inc.)
Abstract Number: 30050
- It has been observed in in vitro studies that this photoimmunotherapy has a dual mechanism of action (MoA): depletion of PD-L1 expressing tumor cells and depletion of PD-L1 expressing immunosuppressive cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). In addition to this dual MoA, the potential for systemic immune checkpoint inhibition was also observed.
- It has been observed in in vivo studies that the treatment resulted in more effective tumor growth suppression compared to anti-PD-L1 antibody alone in an anti-PD-L1 sensitive mouse tumor model and tumor growth suppression compared to saline control in an anti-PD-L1 resistant mouse tumor model.
- It has been observed in in vivo studies that the treatment affects the tumor microenvironment balance by depleting immunosuppressive tumor microenvironment cells and maintains checkpoint inhibition to enhance CD8+ T cell activation.
- RM-0256 was well-tolerated in a GLP toxicity study in which the drug was administered repeatedly to cynomolgus monkeys.
Based on the preclinical study data, Rakuten Medical is currently considering new clinical development opportunities.
About RM-0256
RM-0256 is a conjugate of a newly developed anti-PD-L1 antibody and IRDye®700DX (IR700), a light-activatable dye, that accumulates specifically on PD-L1-expressing cells. PD-L1 is a protein that inhibits the anti-cancer immune response by deactivating killer T cells, via binding to PD-1 which is abundantly expressed on the T cell surface1. PD-L1 is expressed in many solid tumors such as melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck, among others, helping these tumors evade the immune system2. In addition to being present on tumor cells, PD-L1 is also expressed on suppressive immune cells within the tumor microenvironment such as tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs)3. In preclinical studies, PD-L1-targeted photoimmunotherapy resulted in the necrosis of PD-L1 expressing target cells and activation of an anti-cancer immune response. Furthermore, RM-0256 was shown to inhibit the PD-L1:PD-1 interaction, and thus is expected to act systemically as an immune checkpoint inhibitor, further enhancing the anticancer immune response after PD-L1-targeted photoimmunotherapy.
About Rakuten Medical, Inc.
Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing and tumor necrosis. Alluminox therapies have not yet been approved outside of Japan. Rakuten Medical is committed to its mission to conquer cancer by delivering its innovative treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 5 countries/regions, including the United States, where it is headquartered, Japan, Taiwan, Switzerland and India. For more information, visit https://rakuten-med.com/us/
About Alluminox™ platform
The Alluminox™ platform is an investigational technology platform based on a cancer therapy called photoimmunotherapy, which was developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Rakuten Medical is developing the Alluminox platform as a technology consisting of a drug, device, and other related components. The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding. The device component consists of a light source that locally illuminates the targeted cells with light to transiently activate the drug. Pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cancer cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Outside of Japan, Alluminox therapies have not yet been approved by any regulatory authority.
References
1. Chunwan Lu, Priscilla S. Redd, Jeffrey R. Lee, Natasha Savage & Kebin Liu (2016) The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells, OncoImmunology, 5:12, DOI: 10.1080/2162402X.2016.1247135
2. Kythreotou A, Siddique A, Mauri FA, et al. PD-L1Journal of Clinical Pathology 2018;71:189-194. https://jcp.bmj.com/content/71/3/189
3. Shklovskaya, E.; Rizos, H. Spatial and Temporal Changes in PD-L1 Expression in Cancer: The Role of Genetic Drivers, Tumor Microenvironment and Resistance to Therapy. Int. J. Mol. Sci. 2020, 21, 7139. https://doi.org/10.3390/ijms21197139
SOURCE: Rakuten Medical
Post Views: 2,513
