We read with interest the comments of Dr. Grizzi, Dr. Hermonat and Dr. Chiriva-Internati regarding our recent publication1 and are gratified that they regard our study as a significant contribution to the field. Their correspondence provides additional details to supplement the discussions of sperm protein 17 (Sp17) provided in our publication, including citations for some additional publications.
The issue of whether or not Sp17 fits the definition of a cancer-testis (CT) antigen has been addressed in a recent publication from another research group.2 Sp17 expression in cutaneous melanocytic lesions3 as cited in the letter from Grizzi et al. certainly contributes to this debate, as does the expression of Sp17 in motile cilia of normal ciliated epithelium that has been reported in studies by ourselves and others.1, 4, 5, 6 We have unpublished studies demonstrating Sp17 protein expression in cilia of other normal tissues including respiratory epithelium.
However, results that document Sp17 expression in normal tissues do not necessarily serve to argue against Sp17's potential utility as an immunotherapy target. Sp17 is well known for its spontaneous “autoimmunity” in both human subjects and several animal species, but autoimmunity in the form of Sp17 autoantibodies has never been associated with toxicity, with the exception of reversible infertility.7, 8, 9 Therefore, it can be reasonably proposed that clinical trials eliciting enhancement of Sp17-specific immune responses would be similarly associated with minimal toxicity. It should also be noted that the majority of tumor antigens used to date as targets in clinical immunotherapy trials are also self-antigens that exhibit some degree of expression by normal adult tissues. Thus, there should be no major obstacles to clinical trials of Sp17 as an immunotherapy target, despite its expression by a variety of normal tissues.
Nonetheless, as stated in our publication1 and reiterated in the correspondence from Grizzi et al., further characterization of Sp17 function in both normal and malignant cells would be desirable prior to initiation of clinical trials targeting this protein for cancer treatment. Such studies are currently underway in our laboratories and are apparently being pursued by other research groups. Final judgment regarding Sp17's suitability as an immunotherapy target awaits results of these ongoing investigations.