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November 18, 2021/eMedClub News/--Recently, clinical-stage immuno-oncology company CoImmune announced a phase 1/2 clinical trial of an allogeneic CAR-CIK (cytokine-induced killer cell) targeting CD19 The results of the evaluation showed that the drug showed a high degree of safety in children and adult acute lymphoblastic leukemia (ALL) patients after allogeneic hematopoietic stem cell transplantation (HSCT)
.
Among the 21 patients infused in the multicenter dose escalation trial, CARCIK-CD19 cells were derived from human major histocompatibility complex (HLA) identical siblings, matched unrelated and semi-identical donors
.
The results showed that 61.
9% of 21 patients achieved complete remission, with a median follow-up of two years
.
In the highest-dose treatment cohort, 73% of patients had a median overall survival (OS) of 6 months, and 48% of patients had an OS of one year
.
The 6-month and 1-year event-free survival rates (EFS) of the patients were 33% and 22%, respectively
.
In addition, only first-level CRS and syncope associated with DMSO were included in the safety evaluation, and dose-limiting toxicity, neurotoxicity, and graft-versus-host disease (GvHD) were not observed in any patients receiving treatment
.
CoImmune also displayed two other posters at the ASH annual meeting to evaluate the preclinical data of its CAR-CIK technology platform to develop potential treatments for acute myeloid leukemia (AML)
.
In the poster "CD123 and CD33 are co-targeted through the balanced signal on CAR-CIK cells to reduce potential off-target toxicity, while retaining the anti-leukemia activity of acute myeloid leukemia", the researchers demonstrated that the dual concept verification has transactional co-targeting.
The targeted method of stimulation shows high anti-tumor activity against AML while reducing potential off-target toxicity
.
In the poster "Combining the expression of CD33 CAR and CXCR4 to increase the homing of CAR-CIK cells to bone marrow niches and leukemia stem cells to eradicate acute myeloid leukemia", the researchers demonstrated the ability of CXCR4-modified CD33 CAR-CIK to reduce cell infiltration.
The bone marrow niche in the mouse model, which is where the leukemia stem cells are located, usually leads to relapse
.
▲Image source: CoImmune official website "We believe that CAR-CIK cell technology has the potential to improve efficacy while greatly reducing toxicity, because CIK cells have the killing mechanism of T cells and NK cells, and at the same time can resist the induction of GVHD," CoImmune's Chief Executive Officer Dr.
Charles Nicolette said, "Combined with our proprietary non-viral Sleeping Beauty gene transfer technology, this technology may be more effective than recombinant viruses, and we can significantly change the landscape of immuno-oncology
.
Based on these impressive results We are focusing on the advancement of clinical programs for ALL and AML
.
"CIK cell treatment CIK cells, namely cytokine-induced killer cells, refer to mononuclear cells derived from peripheral blood/bone marrow/umbilical blood that pass through a variety of cells in vitro Factors (such as anti-CD3 monoclonal antibodies, IL-2 and IFN-γ, etc.
) stimulate a group of heterogeneous cells obtained after induction and culture
.
The main effector cells of CIK cell therapy are CD3+/CD56+ cells.
Because they express both CD3 and CD56 membrane protein molecules, they are also called NK cell-like T lymphocytes.
They have both powerful anti-tumor activity and NK cells.
The advantages of non-MHC-restricted tumor killing of cells
.
▲ Advantages of CIK cells (picture source: CoImmune official website) CIK cells kill tumor cells through the following mechanisms: (1) bind to target cells and release perforin and granzyme to directly kill target cells; (2) produce a large amount of Cytokines (such as IFN-γ, TNF-α, IL-2, etc.
) indirectly kill tumor cells; (3) regulate the immune system to play an indirect killing effect; (4) induce tumor cell apoptosis and necrosis
.
CIK cells proliferate fast, the main effector cell CD3+/CD56+ cells can proliferate 1000 times; high anti-tumor activity, better than traditional LAK cells, and IL-2 and IFN-γ, etc.
; not restricted by MHC, has a broad spectrum of anti-tumor It is sensitive to multi-drug-resistant tumor cells due to the effect of virus and virus; the current mainstream CIK cell therapy is generally autologous therapy, so the immune response is small and the safety is high; the side effects are small and there are no serious adverse reactions
.
In the production process, the non-viral Sleeping Beauty (SB) transposon can easily construct CIK cells, which can achieve effective anti-leukemia activity with less toxicity
.
Using GMP grade CD19.
CAR/pTMNDU3 and pCMV-SB11 plasmids, CIK cells can be generated from 50ml of donor peripheral blood (PB) by electroporation
.
▲ Simplified manufacturing process (picture source: CoImmune official website) In addition, CAR-CIK technology is expanding its application in the field of solid tumors.
Solid tumors account for 95% of all cancers, compared with B-cell malignancies , CAR-T cells have been shown to have poor efficacy on solid tumors
.
Part of the reason is the suppression of the tumor microenvironment and the risk of major safety issues related to off-target effects
.
CoImmune's innovative technology aims to improve the CAR-CIK function in the tumor microenvironment and increase the persistence of allogeneic cells.
It is possible to make a major breakthrough in the field of solid tumors in the future
.
Reference materials: 1.
https:// -pediatric-and-adult-patients-with-acute-lymphoblastic-leukemia/recommended recent articles
.
Among the 21 patients infused in the multicenter dose escalation trial, CARCIK-CD19 cells were derived from human major histocompatibility complex (HLA) identical siblings, matched unrelated and semi-identical donors
.
The results showed that 61.
9% of 21 patients achieved complete remission, with a median follow-up of two years
.
In the highest-dose treatment cohort, 73% of patients had a median overall survival (OS) of 6 months, and 48% of patients had an OS of one year
.
The 6-month and 1-year event-free survival rates (EFS) of the patients were 33% and 22%, respectively
.
In addition, only first-level CRS and syncope associated with DMSO were included in the safety evaluation, and dose-limiting toxicity, neurotoxicity, and graft-versus-host disease (GvHD) were not observed in any patients receiving treatment
.
CoImmune also displayed two other posters at the ASH annual meeting to evaluate the preclinical data of its CAR-CIK technology platform to develop potential treatments for acute myeloid leukemia (AML)
.
In the poster "CD123 and CD33 are co-targeted through the balanced signal on CAR-CIK cells to reduce potential off-target toxicity, while retaining the anti-leukemia activity of acute myeloid leukemia", the researchers demonstrated that the dual concept verification has transactional co-targeting.
The targeted method of stimulation shows high anti-tumor activity against AML while reducing potential off-target toxicity
.
In the poster "Combining the expression of CD33 CAR and CXCR4 to increase the homing of CAR-CIK cells to bone marrow niches and leukemia stem cells to eradicate acute myeloid leukemia", the researchers demonstrated the ability of CXCR4-modified CD33 CAR-CIK to reduce cell infiltration.
The bone marrow niche in the mouse model, which is where the leukemia stem cells are located, usually leads to relapse
.
▲Image source: CoImmune official website "We believe that CAR-CIK cell technology has the potential to improve efficacy while greatly reducing toxicity, because CIK cells have the killing mechanism of T cells and NK cells, and at the same time can resist the induction of GVHD," CoImmune's Chief Executive Officer Dr.
Charles Nicolette said, "Combined with our proprietary non-viral Sleeping Beauty gene transfer technology, this technology may be more effective than recombinant viruses, and we can significantly change the landscape of immuno-oncology
.
Based on these impressive results We are focusing on the advancement of clinical programs for ALL and AML
.
"CIK cell treatment CIK cells, namely cytokine-induced killer cells, refer to mononuclear cells derived from peripheral blood/bone marrow/umbilical blood that pass through a variety of cells in vitro Factors (such as anti-CD3 monoclonal antibodies, IL-2 and IFN-γ, etc.
) stimulate a group of heterogeneous cells obtained after induction and culture
.
The main effector cells of CIK cell therapy are CD3+/CD56+ cells.
Because they express both CD3 and CD56 membrane protein molecules, they are also called NK cell-like T lymphocytes.
They have both powerful anti-tumor activity and NK cells.
The advantages of non-MHC-restricted tumor killing of cells
.
▲ Advantages of CIK cells (picture source: CoImmune official website) CIK cells kill tumor cells through the following mechanisms: (1) bind to target cells and release perforin and granzyme to directly kill target cells; (2) produce a large amount of Cytokines (such as IFN-γ, TNF-α, IL-2, etc.
) indirectly kill tumor cells; (3) regulate the immune system to play an indirect killing effect; (4) induce tumor cell apoptosis and necrosis
.
CIK cells proliferate fast, the main effector cell CD3+/CD56+ cells can proliferate 1000 times; high anti-tumor activity, better than traditional LAK cells, and IL-2 and IFN-γ, etc.
; not restricted by MHC, has a broad spectrum of anti-tumor It is sensitive to multi-drug-resistant tumor cells due to the effect of virus and virus; the current mainstream CIK cell therapy is generally autologous therapy, so the immune response is small and the safety is high; the side effects are small and there are no serious adverse reactions
.
In the production process, the non-viral Sleeping Beauty (SB) transposon can easily construct CIK cells, which can achieve effective anti-leukemia activity with less toxicity
.
Using GMP grade CD19.
CAR/pTMNDU3 and pCMV-SB11 plasmids, CIK cells can be generated from 50ml of donor peripheral blood (PB) by electroporation
.
▲ Simplified manufacturing process (picture source: CoImmune official website) In addition, CAR-CIK technology is expanding its application in the field of solid tumors.
Solid tumors account for 95% of all cancers, compared with B-cell malignancies , CAR-T cells have been shown to have poor efficacy on solid tumors
.
Part of the reason is the suppression of the tumor microenvironment and the risk of major safety issues related to off-target effects
.
CoImmune's innovative technology aims to improve the CAR-CIK function in the tumor microenvironment and increase the persistence of allogeneic cells.
It is possible to make a major breakthrough in the field of solid tumors in the future
.
Reference materials: 1.
https:// -pediatric-and-adult-patients-with-acute-lymphoblastic-leukemia/recommended recent articles
