"believe results from trials like these wildly vary depending on the mouse models"
You are right. Unlike the previous one, this CEGE pub showed that administering docetaxel shortly after vaccination (within 2 days) but not too much later actually expand the antigen specific T cells. I am not diagreeing with Gold's statement that docetaxel spreads antigen, but I guess Gold could have fielded Monnane's Treg question better and show his depth of knowledge in the field. The following excerpt from a GVAX + Docetaxel animal study provided some evidence of docetaxel actually slightly increased circulating antigen-specific T cells. Sorry to clutter the board. But again, it might not help to promote a competitor..
The combination of a chemotherapeutic agent such as docetaxel with a vaccine like B16.GM could result in chemotherapy-related inhibition of the activation or premature death of immune cells that are stimulated to divide rapidly by the vaccine. A series of studies were conducted to determine whether docetaxel could inhibit antigen (Ag)-specific T cell activation after vaccination with a GM-CSF-secreting tumor cell vaccine. An adoptive T cell transfer system was developed in which OVA is expressed on the surface of the tumor cells (B16.OVA) to serve as a surrogate tumor-associated antigen. Matching, i.e., OVA-expressing, B16.GM vaccine cells (B16.GM-OVA) were also developed. Ovaspecific T-cell receptor transgenic (TCR) precursor frequencies of 2–3% were detected in the spleen and lymph nodes of mice that were adoptively transferred with approximately 1.5•106 OVA-specific T cells only at day 0, and their frequency was unchanged in mice bearing B16-OVA tumors that were treated with either HBSS or docetaxel (Fig. 5a, c). In contrast, a large increase in the fraction of OT-1-specific T cells was seen in the spleens of mice 6 days after vaccination with B16.GM-OVA cells compared to control mice (18% vs. 6% of CD8+ T cells) (Fig. 5a), and a slightly greater, but not significant, expansion was detected in mice treated with the combination of B16.GM-OVA vaccine and docetaxel (22%). By day 10 post-vaccination, the percentage of Ova-specific T cells in mice vaccinated with B16.GM-OVA returned to control levels, whereas the percentage of ova-specific T cells remained slightly elevated in mice treated with the vaccine plus docetaxel (13% vs. 5% in the vaccine-only treatment group).
Pre-vaccination administration of docetaxel, which leads to moderate lymphopenia, might also result in the induction of a stronger anti-tumor T cell response after vaccination. Several studies have shown that a lymphopenic environment, as a result of chemotherapy, radiation therapy or RAG deficiency, is conducive to the expansion and survival of antigen-specific T cells, presumably by eliminating the inhibitory effects of the CD4+CD25+ T regulatory cells [34–37]. However, whether docetaxel increases the potency of GM-CSFsecreting tumor cell vaccines by removal of CD4+CD25+ regulatory T cells or simply reducing tumor burden and increasing antigen accessibility through direct tumor cytolytic effects or by both mechanisms remains to be investigated. In contrast to the observation of Machiels et al. [33], in which post-vaccination administration of paclitaxel did not enhance anti-tumor activity of a vaccine, postvaccination administration of docetaxel in this study significantly increased the survival of mice. The dissimilar outcome may reflect the different timing of chemotherapy treatment. Machiels et al. administered paclitaxel 7 days after vaccination, whereas in our studies docetaxel was administered 2 days after vaccine [33]. It is possible that administration of docetaxel 7 days after vaccination eradicates the rapidly dividing T cells stimulated by the vaccination. However, since docetaxel has a short half-life in vivo [38, 39], residual drug levels will be very low when given 2 days after vaccination, before T cells start their vaccine-induced proliferation. Docetaxel is an approved therapy for prostate cancer, and a GM-CSF-secreting tumor cell vaccine (GVAX) is currently being evaluated in a phase 3 clinical trial in hormone-resistant prostate cancer patients. When undertaking combination therapy with these two treatment modalities for prostate cancer, particular attention should be given to the timing of administration of the two therapies. Docetaxel is typically given every 3 weeks in current treatment regimens, in part to allow for the recovery of drug-induced neutropenia. One could envisage a regimen in which a GM-CSF-secreting tumor cell vaccine such as the GVAX prostate cancer vaccine is administered 2–3 days after each docetaxel treatment. Using this treatment schedule, docetaxel would kill the proliferating tumor cells, increasing antigen accessibility, or remove CD4+CD25+ regulatory T cells or both, but be cleared from the circulation in time to have a minimal effect on the vaccine-induced anti-tumor immune response. The data reported herein demonstrate that administration of docetaxel either prior to or after vaccination enhances the anti-tumor efficacy of the vaccine resulting in prolonged survival at docetaxel dose levels that induce neutropenia. Furthermore, vaccine-induced T cell responses are unaffected by docetaxel administration. These findings provide a rationale for testing docetaxel chemotherapy in combination with GM-CSF-secreting tumor cell vaccines in patients with cancer.