A new perspective on immunotherapy

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.

Chimeric antigen receptor-modified T cells represent a new approach to immune therapy in the treatment of hematologic malignancies. The clinical activity of chimeric antigen receptors (CARs) has been published in acute lymphoblastic leukemia (ALL)and chronic lymphocytic leukemia (CLL).¹ The results have been remarkable, although only a very small number of patients have been treated. We are anticipating further clinical trials and further development of this technology for more wide spread treatment opportunities for patients. The CARs that have been the most successful clinically have a similar basic make-up. They are genetically modified T cells. The T cells are collected from the patients through leukapheresis, then they are genetically
modified to express an extracellular recognition domain that is connected in the intracellular signaling domains of the T cells. Various extracellular recognition domains have been engineered, but the target of CD19 has proven most successful in patients with B cell malignancies, and CD19 is widely expressed on CLL and B-cell ALL. The cells are infused back into the patient, sometimes after undergoing chemotherapy to lymphodeplete the patient (which may improve the recovery and persistence of the cells after treatment). The infusion responses have been
dramatic in some patients, with severe cytokine storm described in reports, usually several days after treatment.² This is thought to reflect the very rapid identification of the target protein and response of the T cells to the target. Those patients with acute leukemia who have responded also appear to respond rapidly, with disappearance of blasts from the peripheral blood within a month. The cells have been detectable in some patients for months after treatment.

Please click here to view the PDF.