While idiotype vaccines have shown promise for B-cell malignancies, production is cumbersome; thus, targeting a common antigen on malignant B cells using an off-the-shelf approach would provide significant logistical advantages.

Bendandi et al demonstrated early on that complete molecular remission in lymphoma patients who had received a patient-specific idiotype vaccine is possible.1  In a follow-up randomized phase 3 study, Schuster et al showed that vaccination with a patient-specific anti-idiotype vaccine led to improved disease-free survival in patients with follicular lymphoma.2  Patients enrolled in study who achieved a complete response to chemotherapy were randomly assigned to vaccine with idiotype conjugated to keyhole limpet hemocyanin (KLH) with local GM-CSF versus KLH control. The median disease-free survival for vaccine-treated patients was 44.2 months versus 30.6 months for patients in the control arm (hazard ratio 0.62; P = .047). However, this patient-specific vaccine required a significant amount of time to produce (6-12 months was allowed). Only 69% of patients randomized remained in complete response to chemotherapy by the time vaccine was available, making the remaining 31% ultimately ineligible to receive vaccine or placebo. Nevertheless, the promising disease-free survival seen among vaccinated patients provides hope that therapeutic vaccines will prove to be a well-tolerated treatment associated with clinical benefit in the setting of minimal disease.

The complexity of making a patient-specific vaccine can lead to significant financial and temporal costs (see figure). The only currently approved therapeutic vaccine for cancer is sipuleucel-T, which showed a statistically significant and clinically meaningful 22% reduction in risk of death in patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer.3  The median 4.1-month improvement in survival was seen without significant side effects (only 1.5% of patients had to stop treatment because of toxicity). However, patients treated with sipuleucel-T must undergo apheresis at 3 time points and the vaccine is subsequently manufactured from the apheresis products at a central processing facility capable of rapid turnaround. This complexity adds to the price of the vaccine: $93 000 US for a complete course of treatment.4  Several off-the-shelf therapeutic vaccines have shown preliminary evidence of efficacy,5–7  providing hope that improvements in patient outcomes with this modality may lead to therapeutic options that are less resource-intense.

Patient-specific therapeutic vaccines are generated from immune cells or tumor material obtained from cancer patients. This process is resource-intensive, but has yielded therapeutic vaccines with clinical benefit. In contrast, large numbers of doses of off-the-shelf vaccines can be manufactured at one time, then stored until needed. In theory, off-the-shelf vaccines should be cheaper to manufacture while simplifying time and supply lines. Professional illustration by Alice Y. Chen.

Patient-specific therapeutic vaccines are generated from immune cells or tumor material obtained from cancer patients. This process is resource-intensive, but has yielded therapeutic vaccines with clinical benefit. In contrast, large numbers of doses of off-the-shelf vaccines can be manufactured at one time, then stored until needed. In theory, off-the-shelf vaccines should be cheaper to manufacture while simplifying time and supply lines. Professional illustration by Alice Y. Chen.

Identification of a common antigen on B-cell malignancies that is not present on normal B cells thus offers the potential for an off-the-shelf vaccine for lymphomas that avoids the resource-intense manufacture and release of patient-specific vaccines. In a convincing set of experiments described in this issue of Blood, Weng et al demonstrate that T-cell leukemia/lymphoma 1 (TCL1) oncoprotein is overexpressed on a wide range of human B-cell lymphomas, but only selectively expressed on normal B cells.8  They demonstrate not only that TCL1 peptide-specific T cells could be generated from normal donors, but that TCL1-specific T cells were present in the blood of patients with lymphoma, and that these T cells could be expanded and, in an HLA-A2–restricted manner, could lyse autologous lymphoma cells but not normal B cells. This approach should help catalyze intensive translational efforts to rationally design off-the-shelf therapeutic vaccines that, alone or in combination with other therapies, can efficiently propel clinically significant antilymphoma immunity in minimal disease settings without significant side effects.

Conflict-of-interest disclosure: The author declares no competing financial interests. ■

REFERENCES

1
Bendandi
 
M
Gocke
 
CD
Kobrin
 
CB
, et al. 
Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma.
Nat Med
1999
, vol. 
5
 
10
(pg. 
1171
-
1177
)
2
Schuster
 
SJ
Neelapu
 
SS
Gause
 
BL
, et al. 
Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma.
J Clin Oncol
2011
, vol. 
29
 
20
(pg. 
2787
-
2794
)
3
Kantoff
 
PW
Higano
 
CS
Shore
 
ND
, et al. 
Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
N Engl J Med
2010
, vol. 
363
 
5
(pg. 
411
-
422
)
4
Gulley
 
JL
Drake
 
CG
Immunotherapy for prostate cancer: recent advances, lessons learned, and areas for further research.
Clin Cancer Res
2011
, vol. 
17
 
12
(pg. 
3884
-
3891
)
5
Vansteenkiste
 
J
Zielinski
 
M
Linder
 
A
, et al. 
Final results of a multi-center, double-blind, randomized, placebo-controlled phase II study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC) [abstract].
J Clin Oncol
2007
, vol. 
25
 
18S
 
Abstract 7554
6
Kantoff
 
PW
Schuetz
 
TJ
Blumenstein
 
BA
, et al. 
Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer.
J Clin Oncol
2010
, vol. 
28
 
7
(pg. 
1099
-
1105
)
7
Butts
 
C
Maksymiuk
 
A
Goss
 
G
, et al. 
Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial.
J Cancer Res Clin Oncol
2011
, vol. 
137
 
9
(pg. 
1337
-
1342
)
8
Weng
 
J
Rawal
 
S
Chu
 
F
, et al. 
TCL1: a shared tumor-associated antigen for immunotherapy against B-cell lymphomas.
Blood
2012
, vol. 
120
 
8
(pg. 
1613
-
1623
)

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