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January 13, 2022 / eMedClub News / -- Recently, Moderna and Carisma announced a partnership to combine Carisama's engineered macrophage technology with Moderna's mRNA and LNP technology to develop in vivo chimeric antigens Receptor macrophage (CAR-M) therapy
.
Under the terms of the agreement, Carisma will receive $45 million in cash upfront and an investment by Moderna in the form of $35 million in convertible notes, and is eligible to receive development, regulatory and commercial milestone payments, as well as net proceeds of any products commercialized under the agreement.
Royalties on sales
.
"Moderna's deep expertise in mRNA and LNP technologies opens up a potentially game-changing opportunity for engineered macrophages," said Steven Kelly, Carisma President and CEO
.
"
Combining Carisma's expertise in engineered macrophage biology Knowledge and Moderna's pioneering in vivo mRNA delivery technology, direct in vivo delivery to monocytes and macrophages, could enable an off-the-shelf therapeutic approach that delivers truly personalized therapy by using the patient's own cells
.
" CAR-M Therapeutics - A New Approach to Treating Solid Tumors CAR (Chimeric Antigen Receptor) technology is a perfect fusion of genetic engineering and immunotherapy, and is one of the most promising research directions in the current field of tumor treatment
.
Unlike other cell types used in CAR cell therapy (e.
g.
T cells, NK cells), macrophages are professional antigen presenting cells capable of activating the patient's own adaptive immune system, which are involved in the innate and adaptive immune responses.
play an important role in
.
In March 2020, the Perelman School of Medicine at the University of Pennsylvania demonstrated the potential of CAR-M therapy in cancer immunotherapy in two different mouse models of metastatic ovarian cancer, showing that CAR-M can overcome cellular Major challenges for therapy in solid tumors
.
▲ Coping with the main challenges in the treatment of solid tumors (Image source: Carisma Therapeutics official website) The emergence of CAR-M has opened up a new way for the treatment of solid tumors: modifying human macrophages with specific CARs to improve the ability of macrophages to treat tumors.
Phagocytosis activity and antigen presentation
.
After CAR-M enters the tumor, it can be activated by the combination of tumor-associated antigens and CAR, signaling through CD3-ζ to phagocytose tumor cells and release cytokines and chemokines, thereby "heating" the tumor microenvironment (TME)
.
Viral-transduced CAR-Ms are locked into a pro-inflammatory M1 phenotype during manufacturing
.
They produce locally acting mediators that reprogram the TME, attract T cells and natural killer (NK) cells, activate nearby antigen-presenting cells (APCs), especially dendritic cells (DCs), and deplete tumor-associated macrophages ( TAM) repolarized to the M1 phenotype
.
In addition to the effect of direct phagocytosis of tumor cells, CAR-M presents the patient's unique neoantigens to T cells, resulting in a broad adaptive immune response, potentially generating long-term immune responses beyond the CAR-targeted antigens
.
▲ The mechanism of action of CAR-M therapy (Source: Carisma Therapeutics official website) The leader of CAR-M therapy—Carisma TherapeuticsCarisma is committed to developing a proprietary cell therapy platform for the differentiation of engineered macrophages, and its pipeline initially focused on oncology.
In early 2021, Carisma initiated the first clinical study of a CAR-M therapy (CT-0508) in patients, achieving a breakthrough milestone in the development of this novel treatment
.
▲ Carisma research pipeline (Image source: Carisma Therapeutics official website) CT-0508 targets human epidermal growth factor receptor 2 (HER2) and is an individualized treatment
.
First, macrophages were extracted from tumor patients, and the adenovirus vector transduction method was used to enable the macrophages to express the specifically recognized CAR.
Finally, the obtained CAR-M was cryopreserved and transported back to the patient for reinfusion
.
In March 2021, Carisma announced the completion of the first patient dosing of CT-0508, ushering in a new era of CAR-M therapy
.
In July of the same year, the US FDA approved the new drug clinical (IND) application for CT-0508
.
Two months later, the U.
S.
FDA granted CT-0508 Fast Track designation for the treatment of patients with solid tumors
.
In December, Carisma announced a clinical research collaboration with Merck & Co.
(MSD) to evaluate CT-0508 in combination with MSD's anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of HER-2-overexpressing solid tumors
.
CT-0508 is currently in Phase 1 clinical development
.
▲ CT-0508 (Image source: Carisma Therapeutics official website) CT-1119 and CT-0729 are both in vitro gene-modified autologous CAR-M therapies
.
CT-1119 targets mesothelin-positive solid tumors and is currently in preclinical development
.
CT-0729 targets prostate-specific membrane antigen for the treatment of metastatic castration-resistant prostate cancer
.
Advantages of CAR-M Therapy Carisma's novel CAR-M platform has the potential ability to reprogram the solid tumor microenvironment, leading to immune activation, T cell recruitment and anti-tumor adaptive immunity
.
Unlike other immune cells, the unique characteristics of CAR-M are key to the success of solid tumor therapy: ➤ Recruit and enter the solid tumor microenvironment with the ability to selectively destroy cancer cells; ➤ Ability to survive in the environment of malignant solid tumors and Maintenance of antitumor phenotype in the presence of immunosuppressive factors; ➤ Activation of adaptive immune responses, resulting in long-term antitumor immunity and prevention of antigen-negative relapse
.
Carisma scientists are expanding the capabilities of engineered macrophages to increase the number of patients who may benefit from this transformative technology
.
Carisma is pushing the boundaries of what is possible by advancing research programs targeting solid tumors and heme malignancies, neurodegeneration and liver fibrosis
.
▲ Other pipelines to be developed (image source: Carisma Therapeutics official website) References: 1.
https://carismatx.
com/technology/2.
https:// -establish-collaboration-to-develop-in-vivo-engineered-chimeric-antigen-receptor-monocytes-car-m-for-oncology/?keywords=RNA
.
Under the terms of the agreement, Carisma will receive $45 million in cash upfront and an investment by Moderna in the form of $35 million in convertible notes, and is eligible to receive development, regulatory and commercial milestone payments, as well as net proceeds of any products commercialized under the agreement.
Royalties on sales
.
"Moderna's deep expertise in mRNA and LNP technologies opens up a potentially game-changing opportunity for engineered macrophages," said Steven Kelly, Carisma President and CEO
.
"
Combining Carisma's expertise in engineered macrophage biology Knowledge and Moderna's pioneering in vivo mRNA delivery technology, direct in vivo delivery to monocytes and macrophages, could enable an off-the-shelf therapeutic approach that delivers truly personalized therapy by using the patient's own cells
.
" CAR-M Therapeutics - A New Approach to Treating Solid Tumors CAR (Chimeric Antigen Receptor) technology is a perfect fusion of genetic engineering and immunotherapy, and is one of the most promising research directions in the current field of tumor treatment
.
Unlike other cell types used in CAR cell therapy (e.
g.
T cells, NK cells), macrophages are professional antigen presenting cells capable of activating the patient's own adaptive immune system, which are involved in the innate and adaptive immune responses.
play an important role in
.
In March 2020, the Perelman School of Medicine at the University of Pennsylvania demonstrated the potential of CAR-M therapy in cancer immunotherapy in two different mouse models of metastatic ovarian cancer, showing that CAR-M can overcome cellular Major challenges for therapy in solid tumors
.
▲ Coping with the main challenges in the treatment of solid tumors (Image source: Carisma Therapeutics official website) The emergence of CAR-M has opened up a new way for the treatment of solid tumors: modifying human macrophages with specific CARs to improve the ability of macrophages to treat tumors.
Phagocytosis activity and antigen presentation
.
After CAR-M enters the tumor, it can be activated by the combination of tumor-associated antigens and CAR, signaling through CD3-ζ to phagocytose tumor cells and release cytokines and chemokines, thereby "heating" the tumor microenvironment (TME)
.
Viral-transduced CAR-Ms are locked into a pro-inflammatory M1 phenotype during manufacturing
.
They produce locally acting mediators that reprogram the TME, attract T cells and natural killer (NK) cells, activate nearby antigen-presenting cells (APCs), especially dendritic cells (DCs), and deplete tumor-associated macrophages ( TAM) repolarized to the M1 phenotype
.
In addition to the effect of direct phagocytosis of tumor cells, CAR-M presents the patient's unique neoantigens to T cells, resulting in a broad adaptive immune response, potentially generating long-term immune responses beyond the CAR-targeted antigens
.
▲ The mechanism of action of CAR-M therapy (Source: Carisma Therapeutics official website) The leader of CAR-M therapy—Carisma TherapeuticsCarisma is committed to developing a proprietary cell therapy platform for the differentiation of engineered macrophages, and its pipeline initially focused on oncology.
In early 2021, Carisma initiated the first clinical study of a CAR-M therapy (CT-0508) in patients, achieving a breakthrough milestone in the development of this novel treatment
.
▲ Carisma research pipeline (Image source: Carisma Therapeutics official website) CT-0508 targets human epidermal growth factor receptor 2 (HER2) and is an individualized treatment
.
First, macrophages were extracted from tumor patients, and the adenovirus vector transduction method was used to enable the macrophages to express the specifically recognized CAR.
Finally, the obtained CAR-M was cryopreserved and transported back to the patient for reinfusion
.
In March 2021, Carisma announced the completion of the first patient dosing of CT-0508, ushering in a new era of CAR-M therapy
.
In July of the same year, the US FDA approved the new drug clinical (IND) application for CT-0508
.
Two months later, the U.
S.
FDA granted CT-0508 Fast Track designation for the treatment of patients with solid tumors
.
In December, Carisma announced a clinical research collaboration with Merck & Co.
(MSD) to evaluate CT-0508 in combination with MSD's anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of HER-2-overexpressing solid tumors
.
CT-0508 is currently in Phase 1 clinical development
.
▲ CT-0508 (Image source: Carisma Therapeutics official website) CT-1119 and CT-0729 are both in vitro gene-modified autologous CAR-M therapies
.
CT-1119 targets mesothelin-positive solid tumors and is currently in preclinical development
.
CT-0729 targets prostate-specific membrane antigen for the treatment of metastatic castration-resistant prostate cancer
.
Advantages of CAR-M Therapy Carisma's novel CAR-M platform has the potential ability to reprogram the solid tumor microenvironment, leading to immune activation, T cell recruitment and anti-tumor adaptive immunity
.
Unlike other immune cells, the unique characteristics of CAR-M are key to the success of solid tumor therapy: ➤ Recruit and enter the solid tumor microenvironment with the ability to selectively destroy cancer cells; ➤ Ability to survive in the environment of malignant solid tumors and Maintenance of antitumor phenotype in the presence of immunosuppressive factors; ➤ Activation of adaptive immune responses, resulting in long-term antitumor immunity and prevention of antigen-negative relapse
.
Carisma scientists are expanding the capabilities of engineered macrophages to increase the number of patients who may benefit from this transformative technology
.
Carisma is pushing the boundaries of what is possible by advancing research programs targeting solid tumors and heme malignancies, neurodegeneration and liver fibrosis
.
▲ Other pipelines to be developed (image source: Carisma Therapeutics official website) References: 1.
https://carismatx.
com/technology/2.
https:// -establish-collaboration-to-develop-in-vivo-engineered-chimeric-antigen-receptor-monocytes-car-m-for-oncology/?keywords=RNA
