A Phase I Trial of T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers

A Phase I Trial of T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers

Publication date: Sep 06, 2021

Background: KK-LC-1 is a cancer germline (CG) antigen with expression restricted to germ cells (which lack MHC class I expression) in adults and epithelial cancers including lung, breast and gastric. This limited expression pattern makes it an ideal target for T Cell Receptor (TCR) gene therapy. TCR T cell therapy targeting CG antigens has been shown to induce objective responses without autoimmunity or off-target toxicity in participants with melanoma, synovial sarcoma and cervical cancer T cells genetically engineered with a TCR targeting KK-LC-1 display specific reactivity against HLA-A01:01, KK-LC-1 target cells. KK-LC-1 TCR T cells can mediate tumor regression in pre-clinical mouse models of cancer Objective: To determine the maximally tolerated dose of KK-LC-1 TCR T cells plus aldesleukin for the treatment of metastatic KK-LC-1 positive epithelial cancers. Eligibility: Participants greater than or equal to 18 years old with metastatic or refractory/recurrent KK-LC-1 positive epithelial cancer. Prior first line systemic therapy is required unless the participant declines standard treatment. Participants must be HLA-A-01:01-positive. Design: This is a phase I clinical trial that will test the safety and efficacy of escalating doses of KK-LC-1 TCR T cells. Participants will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of KK-LC-1 TCR T cells and high-dose aldesleukin. Re-treatment will be allowed for a small number of subjects. ..

Concepts Keywords
Cancer Clinical medicine
Childbearing Medical specialties
Gastric Immunology
Rutgers Cancer treatments
Immune system
Antineoplastic drugs
Interleukin 2
Interleukins
Sjögren syndrome
Chemotherapy
T cell
Radiation
Hybridization
Chemotherapy

Semantics

Type Source Name
disease MESH Cancers
disease MESH autoimmunity
disease MESH melanoma
pathway KEGG Melanoma
disease MESH synovial sarcoma
disease MESH cervical cancer
drug DRUGBANK Aldesleukin
drug DRUGBANK Aspartame
drug DRUGBANK Cyclophosphamide
drug DRUGBANK Fludarabine
disease MESH brain metastases
drug DRUGBANK Creatinine
drug DRUGBANK Hepatitis B Vaccine (Recombinant)
disease MESH hepatitis C
pathway KEGG Hepatitis C
disease MESH fetus
disease MESH immediate hypersensitivity
disease MESH infection
disease MESH congestive heart failure
disease MESH unstable angina pectoris
disease MESH cardiac arrhythmia
disease MESH psychiatric illness
disease MESH pulmonary disease
pathway KEGG Primary immunodeficiency
disease MESH opportunistic infections
disease MESH autoimmune diseases
disease MESH ulcerative colitis
disease MESH rheumatoid arthritis
pathway KEGG Rheumatoid arthritis
disease MESH autoimmune hepatitis
disease MESH pancreatitis
disease MESH Hypothyroidism
disease MESH vitiligo

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *