title: 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-γ 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-γ 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-1α, 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.
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan, USA. luml@karmanos.org
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Lum
authors.forename: Archana
authors.initials: A
authors.lastname: Thakur
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Abhinav
authors.initials: A
authors.lastname: Deol
authors.forename: Zaid
authors.initials: Z
authors.lastname: Al-Kadhimi
authors.forename: Lois
authors.initials: L
authors.lastname: Ayash
authors.forename: Muneer H
authors.initials: MH
authors.lastname: Abidi
authors.forename: Cassara
authors.initials: C
authors.lastname: Pray
authors.forename: Elyse N
authors.initials: EN
authors.lastname: Tomaszewski
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Steele
authors.forename: Dana L
authors.initials: DL
authors.lastname: Schalk
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yano
authors.forename: Alice
authors.initials: A
authors.lastname: Mitchell
authors.forename: Melissa
authors.initials: M
authors.lastname: Dufresne
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Uberti
authors.forename: Voravit
authors.initials: V
authors.lastname: Ratanatharathorn
mesh_terms: D000368:Aged; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014182:Transplantation, Autologous; D017211:Treatment Failure
chemical_list: D018033:Antibodies, Bispecific; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D017252:CD3 Complex; D016207:Cytokines