TY - JOUR
T1 - CD20-targeted T cells after stem cell transplantation for high risk and refractory non-hodgkin's lymphoma
AU - Lum, Lawrence G.
AU - Thakur, Archana
AU - Liu, Qin
AU - Deol, Abhinav
AU - Al-Kadhimi, Zaid
AU - Ayash, Lois
AU - Abidi, Muneer H.
AU - Pray, Cassara
AU - Tomaszewski, Elyse N.
AU - Steele, Patricia A.
AU - Schalk, Dana L.
AU - Yano, Hiroshi
AU - Mitchell, Alice
AU - Dufresne, Melissa
AU - Uberti, Joseph P.
AU - Ratanatharathorn, Voravit
N1 - Funding Information:
Financial disclosure: L.G.L. was supported in part by grants from the Leukemia and Lymphoma Society ( TRP 6066-06 and TRP 6092-09 ), the National Cancer Institute , DHHS ( R01 CA 092344 and R01 CA 140314 ), Michigan Life Sciences (grant number 1819 ), and gifts from the Ruth F. Rattner and the Ann F. & Norman D. Katz Charitable Foundation. Z.A. and A.D. were supported in part by startup funding from the Department Oncology, Wayne State University . The Microscopy, Imaging and Cytometry Resources Core is supported, in part, by NIH Center grant P30CA22453 to The Karmanos Cancer Institute, Wayne State University and the Perinatology Research Branch of the National Institutes of Child Health and Development, Wayne State University.
PY - 2013/6
Y1 - 2013/6
N2 - 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 × 109. 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.
AB - 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 × 109. 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.
KW - Activated T cells
KW - Autologous stem cell transplantation
KW - Bispecific antibody
KW - Non-Hodgkin lymphoma
UR - http://www.scopus.com/inward/record.url?scp=84877888286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877888286&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2013.03.010
DO - 10.1016/j.bbmt.2013.03.010
M3 - Article
C2 - 23529012
AN - SCOPUS:84877888286
SN - 1083-8791
VL - 19
SP - 925
EP - 933
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -