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CD20-targeted T cells after stem cell transplantation for high risk and refractory non-Hodgkin's lymphoma.


ABSTRACT: A phase I trial of infusing anti-CD3 × anti-CD20 bispecific antibody (CD20Bi) armed activated T cells (aATC) was conducted in high-risk/refractory non-Hodgkin's lymphoma patients to determine whether aATC infusions are safe, affect immune recovery, and induce an antilymphoma effect. Ex vivo expanded ATC from 12 patients were armed with anti-CD20 bispecific antibody, cryopreserved, and infused after autologous stem cell transplantation (SCT). Patients underwent SCT after high-dose chemotherapy, and aATC infusions were started on day +4. The patients received 1 infusion of aATC per week for 4 weeks after SCT with doses of 5, 10, 15, and 20 × 10(9). aATC infusions were safe and did not impair engraftment. The major side effects were chills, fever, hypotension, and fatigue. The mean number of IFN-? Enzyme-linked Immunosorbent Spots (ElSpots) directed at CD20 positive lymphoma cells (DAUDI, P = .0098) and natural killer cell targets (K562, P < .0051) and the mean specific cytotoxicity directed at DAUDI (P = .037) and K562 (P = .002) from pre-SCT to post-SCT were significantly higher. The increase in IFN-? EliSpots from pre-SCT to post-SCT in patients who received armed ATC after SCT were significantly higher than those in patients who received SCT alone (P = .02). Serum IL-7, IL-15, Macrophage inflammatory protein (MIP)-1 beta, IP-10, MIP-1?, and Monokine induced by gamma interferone increased within hours after infusion. Polyclonal and specific antibodies were near normal 3 months after SCT. aATC infusions were safe and increased innate and specific antilymphoma cell immunity without impairing antibody recovery after SCT.

SUBMITTER: Lum LG 

PROVIDER: S-EPMC3794673 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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CD20-targeted T cells after stem cell transplantation for high risk and refractory non-Hodgkin's lymphoma.

Lum Lawrence G LG   Thakur Archana A   Liu Qin Q   Deol Abhinav A   Al-Kadhimi Zaid Z   Ayash Lois L   Abidi Muneer H MH   Pray Cassara C   Tomaszewski Elyse N EN   Steele Patricia A PA   Schalk Dana L DL   Yano Hiroshi H   Mitchell Alice A   Dufresne Melissa M   Uberti Joseph P JP   Ratanatharathorn Voravit V  

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20130322 6


A phase I trial of infusing anti-CD3 × anti-CD20 bispecific antibody (CD20Bi) armed activated T cells (aATC) was conducted in high-risk/refractory non-Hodgkin's lymphoma patients to determine whether aATC infusions are safe, affect immune recovery, and induce an antilymphoma effect. Ex vivo expanded ATC from 12 patients were armed with anti-CD20 bispecific antibody, cryopreserved, and infused after autologous stem cell transplantation (SCT). Patients underwent SCT after high-dose chemotherapy, a  ...[more]

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