Translating CAR & TCR Platforms to the Clinic

Juno’s current clinical development program includes trials for both CAR and TCR investigational product candidates targeting B cell lymphomas and leukemias and other hematological malignancies.

TargetProduct CandidateTrial NumberTrial Description
CD19JCAR017NCT02028455A Pediatric and Young Adult Trial of Genetically Modified T Cells Directed Against CD19 for Relapsed/Refractory CD19+ Leukemia
CD19JCAR017NCT02631044A Phase 1, Multicenter, Open-Label Study of JCAR017, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)
CD19JCAR014NCT01865617Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia
WT-1JTCR016 NCT01640301Phase I/II Study of Adoptive Immunotherapy After Allogeneic HCT With Virus Specific CD8+ T Cells That Have Been Transduced to Express a WT1-Specific T Cell Receptor for Patients With High Risk or Relapsed AML, MDS, or CML
WT-1JTCR016NCT02408016Phase I/II Study in WT1-Expressing Non-small Cell Lung Cancer and Mesothelioma, Comparing Cellular Adoptive Immunotherapy With Polyclonal Autologous Central Memory to Naïve CD8+ T Cells That Have Been Transduced to Express a WT1-Specific T Cell Receptor
CD22JCAR018NCT02315612Phase I Dose Escalation Study of Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies
L1-CAMJCAR023NCT02311621A Phase 1 Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Neuroblastoma Using Autologous T-cells Lentivirally Transduced to Express CD171-specific Chimeric Antigen Receptors
ROR-1JCAR024NCT02706392A Phase I Study of Adoptive Immunotherapy for Advanced ROR1+ Malignancies With Defined Subsets of Autologous T Cells Engineered to Express a ROR1-Specific Chimeric Antigen Receptor
MUC16JCAR020NCT02498912A Phase I Clinical Trial of Cyclophosphamide Followed by Intravenous and Intraperitoneal Infusion of Autologous T Cells Genetically Engineered to Secrete IL-12 and to Target the MUC16ecto Antigen in Patients With Recurrent MUC16ecto+ Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

CD19

Our lead CAR T cell product candidates target CD19, a cell surface marker for lymphocytes that is present on most B cell malignancies, including acute lymphoblastic leukemia and various subtypes of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma.

WT-1

Our lead high-affinity TCR T cell product candidate targets WT-1, an intracellular protein that is overexpressed in a number of cancers, including adult myeloid leukemia, or AML, and non-small cell lung, breast, pancreatic, ovarian, and colorectal cancers.

CD22

We are developing CAR T cell product candidate that targets CD22.  Like CD19, CD22 is a cell surface marker for lymphocytes that is present on most B cell malignancies, including acute lymphoblastic leukemia and various subtypes of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma.  Importantly, CD22 expression has been shown to be maintained in acute lymphoblastic leukemia that has lost CD19, making anti-CD22 CAR T cells a potential combination or follow on therapy for CD19 CAR T cells.

L1-CAM

L1CAM, also known as CD171, is a cell-surface adhesion molecule that plays an important role in the development of a normal nervous system. It is overexpressed in neuroblastoma, and there is increasing evidence of aberrant expression in a variety of solid organ tumors, including glioblastoma and lung, pancreatic, and ovarian cancers. Our L1CAM product candidate was originally developed at SCRI.

MUC-16 / IL-12

MUC-16 is a protein overexpressed in the majority of ovarian cancers, but not on the surface of normal ovary cells. CA-125 is a protein found in the blood of ovarian cancer patients that results from the cleavage of MUC-16. CA-125 levels in the blood are a common test for ovarian cancer progression because they correlate with cancer progression. Our MUC-16/IL-12 product candidate, which was originally developed at MSK, has a binding domain that recognizes an extracellular domain of MUC-16 that remains following cleavage of CA-125.  Our MUC-16/IL-12 product candidate is our first development candidate that uses our “armored” CAR technology.

ROR-1

ROR-1 is a protein expressed in the formation of embryos, but in normal adult cells its surface expression is predominantly found at low levels on adipocytes, or fat cells, and briefly on precursors to B cells, or pre-B cells, during normal B cell maturation. ROR-1 is overexpressed on a wide variety of cancers including a subset of non-small cell lung cancer, triple negative breast cancer, pancreatic cancer, prostate cancer, and ALL. It is expressed universally on B cell chronic lymphocytic leukemia and mantle cell lymphoma. Our ROR-1 product candidate was originally developed at FHCRC.