Journal of Immunology Research

Review Article

Overview of Cellular Immunotherapy for Patients with Glioblastoma

Table 4

Active immunotherapy in high grade gliomas using dendritic cells (DCs).


References	Type of trial	Patients	Antigen source	DC maturation	Administration	Immune response	Clinical responses

[54]	Case report	recurrent GBM	Acid eluted peptides from allogenic GBM	none	ID (3 injections)	TI T cells	No survival benefit

[55]	Phase I	progressive HGG 5 GBM, 2 AA, 1 AO after RT and/or CT	Fusion of ATC with DC	none	ID (1 to 7 injections)	Increased CD56 in PBL (4/5) ATR PBMC (6/6) (IFNγ ELISA)	1MR, 4SD (GBM) 2SD (AA, AO)

[56]	Phase I	newly diagnosed HGG: 7 GBM, 2 AA after RT	Antigens eluted from ATC	none	ID (3 injections)	ATR PBMC (4/7) (lytic activity) TI CD4, CD8, CD45RO cells (2/4)	Median survival after IT: 455 versus 257 days (GBM)

[57]	Phase I/II	HGG 7 GBM after RT,3 recurrent GIII	ATC lysates+ KLH	none	ID and/or IC (1 to 10 injections)	DTH (3/6) Increased CD56 (5/5); CD8, CD16, CD19 (4/5) in PBLATR PBMC (2/5) (IFNγ ELISPOT) TI CD4, CD8 cells (2/2)	2 MR, 2SD (GBM), 2SD (GIII) OS > 200 weeks ( ID IC; ID)

[58]	Case report	recurrent GIII	ATC lysates	none	ID (6 injections)	DTH after 2nd vaccination	CR maintained 2 years after IT

[59]	Phase I	HGG 1 GBM, 1 AA, 9 recurrent GBM, 3 recurrent AA	ATC lysates	none	SC (3 injections)	Increased IFNRNA in PBMC (6/10) ATR T cells (4/9) (HER-2, gp100, MAGE-1 tetramers) TI CD8, CD45RO cells (3/6)	Median survival after IT: 133 versus 30 weeks (8 recurrent GBM)

[60]	Phase I	relapsed brain tumours 2 GBM, 1 AA, 4 others Age: < 25 years	ATC RNA	none	ID (3 to 5 injections)	No ATR PBMC (0/3) (IFN ELISA)	1 PR (1XA) 4 SD (1AA, 3 others)
[61]	Phase I	recurrent HGG 11 GBM, 1 PXA	ATC lysates	IL1, TNF, and PGE2	ID (2 to 7 injections)	DTH after 2 vaccinations (6/8) DTH after 5 vaccinations (7/8)	1 PR, 1 SD,1 CR (GBM) 1 CR (PXA) Median OS: 10.5 months 36-month OS: 17%

[62]	Phase I/II	newly diagnosed GBM after RT Vaccine alone () Vaccine and chemotherapy ()	ATC lysates or peptide elutions	none	ID (3 injections)	Vaccine alone: ATR PBMC (4/11) Vaccine and chemotherapy: ATR PBMC (4/13) (lytic activity and IFN Q-PCR)	Vaccine or chemotherapy alone: 2-year survival: 8% Vaccine and chemotherapy: 3 PR - 2-year survival: 42%

[63]	Phase I	recurrent HGG 6 GBM, 7 AA, 2 OAA	Fusion of ATC with DC	TNF	ID (3 injections)	DTH (15/15) ATR PBL (2/8) (lytic activity)	1 SD (GBM), 3 PR, 1 MR (AA)1 PR, 1SD (AOA)

[64]	Phase I	GBM 7 newly diagnosed GBM 5 recurrent GBM	Acid elution from ATC	none	ID (3 injections)	ATR peripheral T cells (6/12) (lytic activity) TI CD8 CD45RO cells (4/8)	1 PR Median OS: 23.4 versus 18.3 months

[65]	Phase I/II	recurrent HGG 18 GBM, 6 GIII after RTnitrosourea	ATC+ KLH	none or OK432	ID (immature or matured DC) IC (immature DC) (1 to 10 injections)	DTH (8/17) ATR PBMC (7/16)(IFN ELISPOT)	1PR, 3MR, 6SD (GBM) 4SD (GIII) Median OS: 480 versus 400 days Longer survival if DC maturation or IC injection

[66]	Phase I	HGG 1 recurrent GBM, 1 recurrent AAafter total resection	Irradiated ATC	Fibroblast transduced TGF/IL4	ID (2 injections)	ATR PBMC (1/1) (EphA2 ELISPOT)	2 PR
[66]	Phase I	HGG 5 newly diagnosed GBM after total resection+RT	ATC lysates	Mixture of TGF/IL4 transduced fibroblasts with DC (IFNγ, IL1β and TNFα)	ID (2 injections)	No response	No response

[67]	Phase I	9 GBM (2 recurrent), 4 AA (3 recurrent)	inactivated ATC	none	ID (2 to 13 injections)	TI CD8 CD45RO T cells (3/3)	12-month survival: 46% 18-month survival or more: 23%

[68]	Phase II	GBM 23 recurrent 11 newly diagnosed	ATC lysates	none	ID (3 to 4 injections)	ATR PBMC (17/34) (IFN PCR)	3 CR, 1 PR Median survival after IT: 642 days versus 430 days

[69]	Phase I/II	recurrent GBM	ATC lysates	IL1, TNF and PGE2	ID (3 to 9 injections ATC lysates)	DTH (9/21 at diagnostic, 2/12 after vaccination)	Median OS: 9.6 months

[70]	Phase I	newly diagnosed GBM	EGFRvIII antigen + KLH	None	ID (3 injections)	DTH EGFRvIII (5/9) DTH KLH (9/9) ATR PBMC (10/12) (EGFRvIII-induced proliferation)	Median OS: 22.8 months

[71]	Phase I	children HGG 23 GBM, 5 AA, 1 OAO, 16 other HGG	ATC lysates + imiquimod	IL1 and TNF	ID (2 to 7 injections) ATC lysates boosts		All HGG: Median OS: 13.5 months GBM alone: Median OS: 12.2 months

[72]	Phase I/II	newly diagnosed GBM (Stupp protocol)	ATC lysates	IL1, TNF, and PGE2	ID (4 injections+ ATC lysates)	DTH (2/5) Increased CD8/CD25 in PBL (6/7) ATR PBMC (5/8) (IFNγ ELISPOT)	Median OS: 24 months

: Abbreviations used in this table: see Table 1 to Table 3; KLH: keyhole limpet haemocyanin; PXA: pleomorphic xanthoastrocytoma; XA: xanthoastrocytoma.