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Biomedical subjects

J A Hank

Publications and source records attributed to J A Hank.

95 records · Page 6Linked to original sources

Alien-driven diversity and alien-selected escape: a rationale for allogeneic cancer immunotherapy.

We have presented two theories relating to the function of histocompatibility antigens and their presence as alien antigens on tumor cells. The theory of alien-driven diversity suggests that the ability to effectively recognize pathogens in the form of "altered-self" derives from prior exposure to antigens cross-reactive with "altered-self" during development. Furthermore, these cross-reactive antigens are alloantigens that are expressed on autologous cells during somatic development. These somatically generated alloantigens could be the result of the same genetic alterations that produced the polymorphism of these antigens within the species. Second, the theory of alien-selected escape suggests that a tumorigenic pathogen selects a cell bearing an alien H* antigen so that the alien-infected cell is recognized as self rather than altered-self by the tumor host. We than summarized data from mouse and man consistent with these theories and with the concept that clinically evident tumors have escaped the host's immune system. Finally, we have discussed potential directions for devising immunotherapy with allogeneic cells that might circumvent the apparent unresponsiveness of the patient's immune system to his own tumor.

Animals↗

Cloned primed-lymphocyte-test reagents in the dissection of HLA-D.

Human T lymphocytes obtained as blasts on day 4 from a primary mixed leukocyte culture (MLC) were cloned in the presence of T cell growth factor (TCGF) and feeder cells. Parameters important in producing higher-specific-activity TCGF were evaluated; irradiation of the responding cells as well as removal of adherent cells or inclusion of indomethacin in the culture was important. In addition, the presence of an irradiated lymphoblastoid cell line (LCL) cell in the TCGF-producing system enhanced activity in the supernate. The long-term maintenance of progeny from clones was achieved by utilizing the LCL autologous with either the responding or sensitizing cells from the initial MLC as feeder cells. Under those conditions, clones could be expanded for 7 or more wk with the maintenance of PLT reactivity. Had all the cells in each clone been maintained for the full 7 wk, more than 1 X 10(10) cells could have been developed in each clone. The cloned reagents provide a higher degree of antigen-specific reactivity than do normal PLT cells. It is to be anticipated that as the requirements for cloning are made more stringent, including the recloning of the cells, these reagents will aid greatly in the dissection of the complexity attendant to HLA-D.

Clone Cells↗

Long-term maintenance of "cloned" human PLT cells in TCGF with LCL cells as a feeder layer.

The long-term maintenance of T cells "cloned" by limiting dilution in TCGF was enhanced by the use of irradiated autologous lymphoblastoid cell line (LCL) cells as well as irradiated LCL cells of the individual to which the T cells were originally primed. It was possible to obtain more than 1 X 10(12) cells from a "clone" seeded at one cell per well. Some of the clones tested express primed LD-typing activity.

Cell Division↗

TCGF production for cloning and growth of functional human T lymphocytes.

In an effort to increase the potency of T cell growth factor (TCGF), several variables were examined for their effects on the production of TCGF. The following manipulations enhanced the potency of TCGF: first, the removal of adherent cells and addition of indomethacin to the producing cultures; second, irradiation with 1000 rads of the cells used to produce TCGF; and, third, the addition of Epstein-Barr virus transformed lymphoblastoid (LCL) cells. It was also noted that the addition of irradiated feeder cells increased the efficiency of limiting dilution cloning.

Cell Division↗