Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.

[liposarcoma]

Adoptive T cell therapy represents an attractive modality for the treatment of patients with cancer . Peripheral blood mononuclear cells have been used as a source of antigen specific T cells but the very low frequency of T cells recognizing commonly expressed antigens such as NY -ESO-1 limit the applicability of this approach to other solid tumors . To overcome this , we tested a strategy combining IL -21 modulation during in vitro stimulation with first -in -class use of tetramer-guided cell sorting to generate NY -ESO-1 specific cytotoxic T lymphocytes (CTL ).CTL generation was evaluated in 6 patients with NY -ESO-1 positive sarcomas , under clinical manufacturing conditions and characterized for phenotypic and functional properties .Following in vitro stimulation , T cells stained with NY -ESO-1 tetramer were enriched from frequencies as low as 0 .4 % to >90 % after single pass through a clinical grade sorter . NY -ESO-1 specific T cells were generated from all 6 patients . The final products expanded on average 1200 -fold to a total of 36 billion cells , were oligoclonal and contained 67 -97 % CD 8 (+), tetramer (+) T cells with a memory phenotype that recognized endogenous NY -ESO-1 .This study represents the first series using tetramer-guided cell sorting to generate T cells for adoptive therapy . This approach , when used to target more broadly expressed tumor antigens such as WT-1 and additional Cancer -Testis antigens will enhance the scope and feasibility of adoptive T cell therapy .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated