Tumor Antigens May Be Induced by Viruses

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In contrast to chemically induced tumors, virally induced tumors express tumor antigens shared by all tumors induced by the same virus. For example, when syngeneic mice are injected with killed cells from a particular polyoma-induced tumor, the recipients are protected against subsequent challenge with live cells from any polyoma-induced tumors (see Table 22-2). Likewise, when lymphocytes are transferred from mice with a virus-induced tumor into normal syngeneic recipients, the recipients reject subsequent transplants of all syngeneic tumors induced by the same virus. In the case of both SV40- and polyoma-induced tumors, the presence of tumor antigens is related to the neoplastic state of the cell. In humans, Burkitt's-lymphoma cells have been shown to express a nuclear antigen of the Epstein-Barr virus that may indeed be a tumor-specific antigen for this type of tumor. Human papilloma virus (HPV) E6 and E7 proteins are found in more than 80% of invasive cervical cancers—the clearest example of a virally encoded tumor antigen. Consequently, there is great interest in testing as vaccine candidates the HPVs that are strongly linked to cervical cancer, such as HPV-16.

The potential value of these virally induced tumor antigens can be seen in animal models. In one experiment, mice immunized with a preparation of genetically engineered polyoma virus tumor antigen were shown to be immune to subsequent injections of live polyoma-induced tumor cells. In another experiment, mice were immunized with a vaccinia-virus vaccine engineered with the gene encoding the polyoma-tumor antigen. These mice also developed immunity, rejecting later injections of live polyoma-induced tumor cells (Figure 22-9).

Elute Q U Q peptide Q

Melanoma tumor cells

Elute Q U Q peptide Q

Purify -> peptides HPLC

Sequence peptides

Melanoma tumor cells

Tumor-cell cDNA library

Plasmid DNA

Monkey kidney cos cells

Tumor-cell cDNA library replication large-T antigen

Plasmids replicate (104-105 copies of cDNA)

Plasmid DNA

Monkey kidney cos cells

Plasmids replicate (104-105 copies of cDNA)

replication large-T antigen

| Two methods used to isolate tumor antigens that induce tumor-specific CTLs. See text for details.

FIGURE 22-8

Recombinant PV tumor antigen

Live PV-induced tumor cells

Recombinant PV tumor antigen

No tumor

No tumor

FIGURE 22-9

Experimental induction of immunity against tumor cells induced by polyoma virus (PV) has been achieved by immunizing mice with recombinant polyoma tumor antigen (a), with a vaccinia vector vaccine containing the gene encoding the PV tumor antigen (b), or with CTLs specific for the PV tumor antigen (c). Unimmunized mice (d) develop tumors when injected with live polyoma-induced tumor cells, whereas the immunized mice do not.

Vaccinia virus vector-PV tumor antigen

Live PV-induced tumor cells

Vaccinia virus vector-PV tumor antigen

Isolate and clone CTLs specific for PV tumor antigen

Live PV-induced tumor cells

Isolate and clone CTLs specific for PV tumor antigen

Live PV-induced tumor cells

Syngeneic recipient

No tumor

Syngeneic recipient

No tumor

No tumor

No tumor

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Responses

  • TEMSHE
    What is killed cell from a particular polyoma induced tumor?
    4 years ago

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