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424 Part V: Therapeutic Principles Chapter 27: Vaccine Therapy 425

50 One strategy is to vaccinate patients after chemotherapy, when a state
of minimal residual disease has been achieved. Moreover, lymphope-
UPN Postvaccine
nia induced by chemotherapy can also enhance antitumor immunity by
40 6 promoting expansion of vaccine-induced effector T cells and minimiz-
33
8 ing tumor-induced immune suppression. In this setting, the profound
15
lymphopenia from chemotherapy results in release of cytokines, such as
Specific lysis (%) 30 16 IL-15, providing a powerful proliferative drive to lymphocytes, which
19
could be exploited to increase specific lymphocyte responses to the
23
vaccine. Moreover, this strategy can eradicate cells that suppress antitu-
mor responses such as regulatory T cells, and may overcome inherent
20
defects in T-cell signaling, processing, or presentation. In addition,
33
the afferent phase of the immune response could be enhanced by using
10 more potent vaccines with novel adjuvants such as toll-like receptor
ligands, or by vaccinating donors of transplant recipients who have a
Maximum level healthy immune system as opposed to patients who may be immuno-
reached prevaccine
41
0 compromised either from the cancer or from therapy. Alternatively,
0 12.5 25 50 100 vaccines could be used in combination with agents that inhibit immu-
Effector-to-target ratio nosuppressive mechanisms, such as immune checkpoint receptors/lig-
43
42
ands and/or deplete regulatory T cells, to augment the afferent and/
Figure 27–2. T-cell–mediated lysis of human autologous lymphoma or effector phase of the immune response. The use of these agents in
cells after vaccination with idiotype keyhole limpet hemocyanin (KLH) combination with therapeutic cancer vaccines may lead to enhanced
protein plus granulocyte-monocyte colony-stimulating factor (GM-CSF). antitumor immunity and improved clinical outcome.
Representative results are shown from six individual patients, desig-
nated by unique patient number (UPN). (Adapted with permission from
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