Page 398 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

376 PART IV Specific Malignancies in the Small Animal Patient

into the skin or muscle with an intradermal or intramuscular injec- utilizing various xenogeneic melanosomal antigens as DNA (or
tion. Once in the skin or muscle, professional antigen-presenting peptide with adjuvant) vaccination have begun and the prelimi-
nary results look favorable.
197,211,212
cells, particularly dendritic cells, are able to present the transcribed
VetBooks.ir and translated antigen in the proper context of major histocom- treatment of canine oral melanoma has been shown in clinical tri-
Further evidence for the efficacy of immunotherapy for the
patibility complex and costimulatory molecules. Although DNA
vaccines have induced immune responses to viral proteins, vacci- als with the CSPG4 vaccination. 184,213 In a controlled prospective
nating against tissue-specific self proteins on cancer cells is clearly study of dogs with stage II or III oral MM, 19 dogs were treated
a more difficult problem. One way to induce immunity against a with surgical resection only and 23 dogs were treated with surgical
tissue-specific differentiation antigen on cancer cells is to vaccinate resection and adjuvant CSPG4 vaccination. The outcomes were
with xenogeneic antigen or DNA that is homologous to the cancer significantly better in the vaccinated group. The median disease-
antigen. Vaccination with DNA encoding cancer differentiation free interval, MST, and 1- and 2-year survival rates in the vac-
antigens is ineffective when self DNA is used, but tumor immu- cinated group were 477 days, 684 days, and 73.9% and 30.4%,
nity can be induced by orthologous DNA from another species. 194 respectively, compared with 180 days, 200 days, and 26.3% and
A xenogeneic DNA vaccine program for melanoma was devel- 5.3%, respectively, in the nonvaccinated group. 184
oped in collaboration with human investigators from Memorial The role of xenogeneic DNA vaccination in the adjuvant man-
Sloan-Kettering Cancer Center. 195,196 Preclinical and clinical agement of dogs with digit MM has also been investigated. 214 A
studies showed that xenogeneic DNA vaccination with tyrosi- staging scheme was developed based on tumor size, tumor depth,
nase family members (e.g., tyrosinase, GP100, GP75) produced bone involvement, and presence of nodal and distant metastatic
immune responses resulting in tumor rejection or protection disease. A T1 digit melanoma was defined as less than 2 cm diam-
with prolonged survival times, whereas syngeneic vaccination eter and superficial or exophytic; a T2 tumor was defined as 2 to
with orthologous DNA did not induce an immune response. 197 5 cm in diameter with minimal invasion; a T3 digit melanoma
Although tyrosinase may not appear to be a preferred target in was defined as greater than 5 cm or invading the subcutaneous tis-
amelanotic canine melanoma because of poor expression when sue; and a T4 tumor was defined as invading into fascia or bone.
assessed by IHC, more appropriate and/or sensitive PCR-based Stage I was defined as nonmetastatic T1 digit melanoma; stage II
32
studies and other IHC-based studies document significant tyrosi- as nonmetastatic T2 digit melanoma; stage III as nonmetastatic
nase overexpression in melanotic and amelanotic melanomas T3 or T4 digit melanoma and/or LN metastasis; and stage IV
across species. 16,39,198–201 These studies provided the impetus for was defined as distant metastasis. 214 Treatment of dogs with digit
development of a xenogeneic tyrosinase DNA vaccine program melanoma with digit amputation and adjuvant Oncept resulted
in canine MM. The antibody and T-cell responses in dogs vacci- in significantly improved outcomes compared with historical out-
nated biweekly for a total of four vaccinations with human tyrosi- comes with digit amputation only. 214 Dogs presenting with meta-
nase (huTyr) demonstrated antigen-specific IFN-γ T-cells with static disease had a significantly worse MST (105 days) than dogs
2- to 5-fold increases in circulating antibodies to huTyr which can without evidence of metastatic disease at presentation (533 days),
cross react to canine tyrosinase, suggesting the breaking of toler- with a 3-year survival rate of 48% in the latter group. The clinical
ance. 202,203 The clinical results with prolongation in survival have staging scheme was also prognostic, with MSTs of greater than
been reported previously. 195,196 952 days, greater than 1093 days, 321 days, and 76 days for dogs
The results of these trials demonstrate that xenogeneic DNA with stage I, II, III, and IV disease, respectively. 214
vaccination in canine MM: (1) is safe; (2) leads to the develop-
ment of antityrosinase antibodies and T cells; (3) is potentially References
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