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Irradiation of umbilical cord blood derived Lymphokine Activated Killer (LAK) cells prevents GVHD while maintaining an antitumor effect in vivo
Author(s) -
Mittal Amit K,
Clark Erin M,
Joshi Deepa S,
Grimm Andrew B,
Gordon Bruce,
Coccia Peter,
Joshi Shantaram S
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a229-b
Subject(s) - lymphokine activated killer cell , bone marrow , peripheral blood mononuclear cell , immunology , haematopoiesis , cytotoxicity , lymphocyte , cancer research , medicine , cord blood , umbilical cord , in vitro , chemistry , immune system , stem cell , biology , t cell , interleukin 21 , biochemistry , genetics
Umbilical cord blood (UCB) is an alternative source of cells for transplantation. Compared to peripheral blood or bone marrow there is an observed lower incidence of graft‐versus‐host disease (GVHD) when UCB is used, although UCB can still cause significant GVHD. Abrogation of GVHD without compromising the graft‐versus‐tumor (GVT) effect is challenging. In this study, we have investigated the efficacy of irradiation of LAK cells from UCBC with doses sufficient to inhibit their proliferation but not their antitumor cytotoxicity. UCB mononuclear cells were stimulated with 1000 U/mL IL‐2 to generate LAK cells, which demonstrated significant cytotoxicity against both lymphoma (Granta‐519) and neuroblastoma (IMR‐32) when compared to non‐stimulated cells (p<0.001). Irradiation of LAK cells with a dose of 17 Gy significantly inhibited their proliferation compared to non‐irradiated cells (p=0.035), while maintaining their antitumor cytotoxicity in vitro. Weekly injections of irradiated LAK cells into NOD/SCID mice bearing target tumor showed a significant survival advantage compared to untreated control animals (p= 0.031). Animals who received non‐irradiated cells showed extensive GVHD after 7 injections, evidenced by marked alopecia. Histological analysis revealed extensive lymphocyte infiltration in the skin and intestine. Whereas, there was no evidence of GVHD in animals that received irradiated cells. Thus our studies indicate that the administration of irradiated LAK effector cells is effective in conferring a GVT effect without causing GVHD.