Details

Autor(en) / Beteiligte

• Straathof, Karin
• Flutter, Barry
• Wallace, Rebecca
• Jain, Neha
• Loka, Thalia
• Depani, Sarita
• Wright, Gary
• Thomas, Simon
• Cheung, Gordon Weng-Kit
• Gileadi, Talia
• Stafford, Sian
• Kokalaki, Evangelia
• Barton, Jack
• Marriott, Clare
• Rampling, Dyanne
• Ogunbiyi, Olumide
• Akarca, Ayse U
• Marafioti, Teresa
• Inglott, Sarah
• Gilmour, Kimberly
• Al-Hajj, Muhammad
• Day, William
• McHugh, Kieran
• Biassoni, Lorenzo
• Sizer, Natalie
• Barton, Claire
• Edwards, David
• Dragoni, Ilaria
• Silvester, Julie
• Dyer, Karen
• Traub, Stephanie
• Elson, Lily
• Brook, Sue
• Westwood, Nigel
• Robson, Lesley
• Bedi, Ami
• Howe, Karen
• Barry, Ailish
• Duncan, Catriona
• Barone, Giuseppe
• Pule, Martin
• Anderson, John

Titel

Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma

Ist Teil von

• Science translational medicine, 2020-11, Vol.12 (571)

Ort / Verlag

United States

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The reprogramming of a patient's immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥10 /meter CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity.