The following excerpts were taken from a recently published study by Schlom et al. that looked at a cancer vaccine plus docetaxel.  Key points are that the docetaxel needs to given after the vaccine, the docetaxel causes an antigen cascade effect and that there is no impact of docetaxel on Tregs.  Recall that Mitch Gold said at the BIO/CEO conference last year when talking about Provenge plus Taxotere,

 “Sequence these agents in the right order you’re going to start to get really dramatic increases in survival and we saw evidence of a median survival benefit of anywhere from 9 to 14 months with Provenge followed by Taxotere”

Excerpts from, “Combination of Docetaxel and Recombinant Vaccine Enhances T-cell Responses and Antitumor Activity: Effects of Docetaxel on Immune Enhancement”  Garnett, Schlom and Hodge, June 1, 2008

Vaccine induced immune responses mediated by a live vector in the

studies reported here were enhanced when docetaxel was given

after vaccine and diminished when the drug was given before or

concurrently with vaccine (Fig. 3). Although the dose sequencing

in our studies was different from that of previously reported

studies (18), our findings confirm that chemotherapy given at

optimal times enhances immune responses to vaccine...

A recent clinical study (28) by Arlen et al. reported prolonged

time to progression in crossover patients who received

docetaxel after vaccine (6.1months) compared with patients

who received docetaxel and vaccine concurrently (3.2 months).

In addition, progression-free survival increased in the crossover

group compared with historic controls from the same

institution and same patient population who received docetaxel

alone (3.7 months; ref. 28)...

The combination of docetaxel and vaccine in the studies

reported here not only enhanced CD4+ T-cell responses

in tumor-bearing mice (Fig. 6A) but also led to a broadening of immune responses,

as indicated by CD8+ T-cell responses to

antigens within the tumor but not encoded within the vaccine

(Fig. 6C); the combination of docetaxel and vaccine produced a

greater antigen cascade than either modality alone...

A clinical study in patients with metastatic breast cancer showed

that, in humans, paclitaxel and docetaxel can increase IFN-g,

IL-6, and GM-CSF, as well as MLR (mixed lymphocyte reaction), natural killer, and

lymphokine-activated killer cell activity (35)...

However, the combination

of docetaxel and vaccine increased antigen-specific T-cell

responses to both the antigen in the vaccine and tumor-derived

cascade antigens. Docetaxel, unlike cyclophosphamide, did not

inhibit Treg function. Thus, patients who show no objective

clinical response to docetaxel alone may still benefit from the

ability of the drug to enhance immune responses and thus

potentiate patient benefit from vaccine therapy.

These studies show for the first time that in non–tumorbearing

mice (a) docetaxel modulates CD4+, CD8+, CD19+,

natural killer cells, and Treg populations; (b) unlike cyclophosphamide,

docetaxel does not inhibit the function of

Tregs; and (c) docetaxel enhances CD8+ function...

These studies were conducted in non–tumor-bearing mice to rule

out indirect evidence of docetaxel on tumor. Studies with

tumor-bearing mice show for the first time that (a)

administering docetaxel after recombinant poxviral vaccines

results in optimal enhancement of vaccine-specific immune

responses; (b) the combination of docetaxel and recombinant

poxviral vectors is more effective than either agent alone at

reducing tumor burden; and (c) the combination of docetaxel

and vaccine induces antigen-specific T-cell responses to tumor derived

antigens distinct from the antigen used in the vaccine

(antigen cascade). These findings thus have important

implications for the combined use of vaccines and chemotherapeutic

agents in the clinic.