Abstract
Peripheral blood lymphocytes (PBL) from a patient with poorly differentiated lymphocyte lymphoma (PDLL), after stimulation for 7 days with X-irradiated allogeneic lymphocytes pooled from three or ten donors (poolx), were cytotoxic for autologous lymphoma cells. Some clones lytic for autologous lymphoma cells, that were derived from this patient's pool-stimulated cells, resembled cytotoxic T lymphocytes (CTL), while other clones resembled natural killer (NK)-like cells in that they also lysed NK-sensitive HLA-negative K562 cells. In a second patient with more advanced PDLL, PDL cultured with T-cell growth factor (which is produced following stimulation with mitogens or alloantigens) lysed autologous lymphoma cells. On the basis of these in vitro findings, we asked whether IV transfusions with X-irradiated allogeneic leukocytes would result in anti-lymphoma responses in vivo. Ten days after transfusions with X-irradiated leukocytes from four unrelated donors, the first patient's two previously palpable nodes were no longer palpable and he remained in complete clinical remission for 6 months. The second patient had a temporary partial remission with dramatic reduction in size of multiple cervical and axillary nodes within 2 weeks after receiving the leukocyte transfusions.
Keywords: Growth Factor, Lymphoma, Cancer Research, Natural Killer, Axillary Node
References
- 1.Bach ML, Bach FH, Zarling JM. Pool-priming: A means of generating T lymphocytes cytotoxic to tumour or virus-infected cells. Lancet. 1978;I:20. doi: 10.1016/s0140-6736(78)90364-1. [DOI] [PubMed] [Google Scholar]
- 2.Bach FH, Inouye H, Hank JA, Alter BJ. Human T lymphocyte clones reactive in primed lymphocyte typing and cytotoxicity. Nature. 1979;281:307. doi: 10.1038/281307a0. [DOI] [PubMed] [Google Scholar]
- 3.Bear RH, Roholt OA, Pressman O. Protection against syngeneic tumor grafts induced by inoculation with normal allogeneic tissues. Immunol Commun. 1977;6:547. doi: 10.3109/08820137709093465. [DOI] [PubMed] [Google Scholar]
- 4.Bessis M, Daussett J. Etude critique des remissions en cours des leucémies aigües traitées par exsanguino-transfusion. (Comparison avec les remissions spontanées et celles induites par les antagonistes de l'acide folique) Rev Hemat. 1950;5:188. [PubMed] [Google Scholar]
- 5.Bessis M, Bernard J (1983) Remissions after exchange transfusions in acute leukemia. On the possible antileukemic properties of normal blood. Historical notes and recent reflections. Blood Cells (in press) [PubMed]
- 6.Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon: Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982;155:1823. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Hersey P, Bindon C, Edwards A, Murray E, Phillips G, McCarthy BJ. Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin-2. Int J Cancer. 1981;28:695. doi: 10.1002/ijc.2910280607. [DOI] [PubMed] [Google Scholar]
- 8.Hurrell S, Zarling JM (1983) Ly2+ effectors cytotoxic for syngeneic tumor cells: generation by allogeneic stimulation and by supernatants from mixed leukocyte cultures. J Immunol (in press) [PubMed]
- 9.Levinthal BG, Konior GS. Immunologic treatment of neoplasmas in man. In: Green I, Cohen S, McClusky RT, editors. Mechanisms of tumor immunity, vol 215. New York: John Wiley & Sons; 1977. p. 250. [Google Scholar]
- 10.Parmiani G, Sensi ML, Carbone G, et al. Cross-reactions between tumor cells and allogeneic normal tissues. Inhibition of syngeneic lymphoma outgrowth in H-2 and non-H-2 alloimmune Balb/c mice. Int J Cancer. 1982;29:323. doi: 10.1002/ijc.2910290316. [DOI] [PubMed] [Google Scholar]
- 11.Seeley JK, Golub SH. Studies on cytotoxicity generated in human MLC. I. Time course and target spectrum of several distinct concomitant cytotoxic activities. J Immunol. 1978;120:1415. [PubMed] [Google Scholar]
- 12.Strausser JL, Mazumder A, Grimm EA, Lotze MT, Rosenberg SA. Lysis of human solid tumors by autologous cells sensitized in vitro to alloantigens. J Immunol. 1981;127:266. [PubMed] [Google Scholar]
- 13.Zarling JM, Bach FH. Sensitization of lymphocytes against pooled allogeneic cells. I. Generation of cytotoxicity against autologous human lymphoblastoid cell lines. J Exp Med. 1978;147:1334. doi: 10.1084/jem.147.5.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Zarling JM, Robins HI, Raich PC, Bach FH, Bach ML. Generation of cytotoxic T lymphocytes to autologous human leukemia cells by sensitization to pooled allogeneic normal cells. Nature. 1978;274:269. doi: 10.1038/274269a0. [DOI] [PubMed] [Google Scholar]
- 15.Zarling JM, Bach FH, Kung P. Sensitization of lymphocytes against pooled allogeneic cells. II. Characterization of effector cells cytotoxic for autologous lymphoblastoid cell lines. J Immunol. 1981;126:375. [PubMed] [Google Scholar]