Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study.
Allogeneic cell therapy (allo-CT) is emerging as an effective treatment for patients relapsing after allogeneic bone marrow transplantation (BMT), indicating that tumor cells resisting chemoradiotherapy may still respond to immunocompetent allogeneic lymphocytes. We investigated possible graft-versus-tumor (GVT) effects in six patients with metastatic breast cancer that would be comparable to the graft-versus-leukemia (GVL) phenomenon occurring after allogeneic BMT in hematologic malignancies. The patients were cytoreduced with high-dose chemotherapy and autologous stem cell transplantation (ASCT), and were treated ambulatory with allo-CT consisting of adoptive transfer of HLA-matched donor peripheral blood lymphocytes (PBL) activated in vivo with human recombinant interleukin-2 (rIL-2). If no graft-versus-host disease (GVHD) developed, allo-CT was augmented with infusion of donor PBL, preactivated in vitro with rIL-2. Treatment was well tolerated, with low therapy-related toxicity in all patients. Two patients developed signs and symptoms compatible with GVHD grade I-II, one of whom shows no evidence of disease at more than 34 months out. In the remaining patients, progression-free survival following allo-CT ranged between 7 and 13 months. Allogeneic cell-mediated, cytokine-activated immunotherapy might be utilized for induction of GVT in metastatic breast cancer. A search for techniques to boost chimerism without severe GVHD is indicated.
Or
R
R
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel. reuvenor@hadassah.org.il
Ackerstein
A
A
Nagler
A
A
Kapelushnik
J
J
Naparstek
E
E
Samuel
S
S
Amar
A
A
Bruatbar
C
C
Slavin
S
S
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001781:Blood Component Removal; D001943:Breast Neoplasms / Q000628:therapy*; D018567:Breast Neoplasms, Male / Q000628:therapy*; D002678:Chimera; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin