The effect of purification on the immunogenicity of tumor-specific transplantation antigens (original) (raw)

Summary

Immunization with the tumor-specific transplantation antigens (TSTA) of experimental, chemically induced sarcomas engenders specific host resistance to challenge with viable, homotypic neoplastic cells. The strength of tumor resistance depends upon the physical state of the TSTA used for immunization. Treatment with 105–106 irradiated tumor cells, a 2-log dose range, induces complete rejection of neoplastic challenges, while immunization within a 1-log dose range with crude 3 M KCl or with 2.5% butanol extracts containing TSTA evokes a weak state of resistance characterized by decreased outgrowth of tumor challenges, but not neoplastic regression. The reduced immunogenicity may be due to either contamination with substances that antagonize host resistance, for example by induction of suppressor cells, or an intrinsic limitation by virtue of the molecular properties of extracted compared with cell-surface TSTA. MCA-F and MCA-D, two noncross-reactive fibrosarcomas induced in C3H/HeJ mice with 3-methylcholanthrene, were employed to compare the relative immunogenic activity of intact tumor cells, 2.5% butanol extracts, and materials sequentially purified by preparative isoelectric focusing (pIEF), preparative isotachophoresis (pITP), and high performance gel permeation chromatography (HPGPC). Immunoprotective TSTA activity purified 50,000-fold by this protocol extended the effective dose range by four to five logs: 15 pg to 1.5 μg MCA-F or 1 pg to 10 ng MCA-D antigen-induced specific host resistance. However, despite the appreciable purification of TSTA, immunization with extracted materials only delayed neoplastic outgrowth. They induced neither immediate rejection nor only temporary progression of transplanted tumor cells. Thus, purified TSTA preparations by themselves lack the immunogenic properties of intact cells that result in maximal induction of tumor resistance.

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Article Open access 29 September 2022

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Author notes

  1. Thomas L. Saunders
    Present address: Immunobiology Research Center, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, 55455, Minneapolis, Minnesota, USA

Authors and Affiliations

  1. Division of Immunology and Organ Transplantation, Department of Surgery, Department of Pathology, The University of Texas Medical School and Graduate School of Biomedical Sciences, 77030, Houston, Texas, USA
    Thomas L. Saunders, Barry D. Kahan & Neal R. Pellis

Authors

  1. Thomas L. Saunders
  2. Barry D. Kahan
  3. Neal R. Pellis

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Saunders, T.L., Kahan, B.D. & Pellis, N.R. The effect of purification on the immunogenicity of tumor-specific transplantation antigens.Cancer Immunol Immunother 19, 22–27 (1985). https://doi.org/10.1007/BF00199307

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