Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines

Figures & data

Figure 1. Manufacturing of dendritic cell-autologous tumor antigen (DC-ATA) vaccine.

Table 1. Summary of clinical trials in which patients were treated with personal dendritic cell-autologous tumor antigen (DC-ATA) vaccines.

	RCC	Mel	Mel	HCC	GBM	Ovary
ClinicalTrials.gov NCT	00014131	00012064	00436930	None	03400917	00331526
Trial Phase	1–2	1–2	Random 2	1	2	Random 2
Study population	Metastatic	Advanced regional or Distant Metastatic	Advanced regional or Distant Metastatic	HBV+ locally advanced	Newly Diagnosed	Newly Diagnosed Stage 3 or 4
Treatment type	Monotherapy	Monotherapy	Monotherapy	Adjuvant	Adjuvant	Adjuvant
Number Treated	9	54	18	8	57	28
Vaccine Adjuvant	GM-CSF	GM-CSF	GM-CSF	GM-CSF	GM-CSF	GM-CSF
Accrual Started	09/2001	11/2000	10/2007	01/2013	08/2018	12/2017
First Dose Injected	10/2001	01/2001	11/2007	04/2013	11/2018	08/2018
Last Dose Injected	09/2006	09/2005	08/2011	10/2013	09/2020	02/2022
Last Date of Follow Up	05/2008	12/2011	12/2016	11/2013	01/2023	03/2022
Duration of Injections	6 mos	6 mos	6 mos	1 mos	6 mos	6 mos
Average # of Injections	6.4/8	7.4/8	7.1/8	3.0/3	6.9/8	7.4/8
Last Dose Injected	2007	2007	2011	2013	2021	2022
Immune Response	Yes^Citation1	Yes^Citation1	Yes^Citation2	N/A	Yes^Citation3	N/A
Tumor Response^Citation4	2/7	0/15	1/8	N/A	N/A	N/A
PFS median in mos.	1.9	4.2	5.4	N/A	10.4	18.8
OS median in mos.	26.1	>60	43.4	N/A	16.0	NR
2-y overall survival	67%	72%	68%	N/A	91%	33%

¹by changes in delayed type hypersensitivity to irradiated tumor cells.

²by changes in serum cytokines.

³by changes in interferon gamma ELISpots.

⁴includes delayed tumor responses.

GM-CSF=granulocyte-macrophage colony stimulating factor.

PFS=progression free survival; OS=overall survival.

DC-ATA=dendritic cell-autologous tumor antigens. DC were incubated with whole irradiated autologous tumor cells or with a tumor cells lysate from autologous irradiated tumor cells.

PFS=progression free survival.

N/A=not available.

NR=not reached.

Table 2. Summary of adverse events reported in DC-ATA clinical trials in which up to 8 doses were injected.

	Mel DC-ATA	Mel DC-ATA	Ovary DC-ATA	GBM DC-ATA	Mel TC	Ovary MC
Number of Subjects	54	18	28	57	24	16
Average # of Vaccinations	7.4	7.1	7.4	6.9	6.2	7.3
SAE attributed to study agent	2	0	0	0	0	1
Stopped RX because of AE	0	0	0	0	0	0
Highest AE Grade 0	0%	22%	4%	54%	8%	0%
Highest AE Grade 1	19%	61%	18%	42%	21%	31%
Highest AE Grade 2	56%	11%	54%	4%	71%	38%
Highest AE Grade 3	19%	5%	29%	0	0%	31%
Highest AE Grade 4	4%	0	0	0	0	0
Local Injection Site Reaction	80%	67%	54%	16%	67%	69%
Flu-like Symptoms	15%	28%	32%	11%	38%	19%
Malaise/Fatigue	19%	0%	50%	0%	21%	38%
Bone Discomfort	48%	17%	32%	7%	17%	19%
Rash/Pruritus	41%	6%	32%	4%	8%	44%

Mel= melanoma; GBM=glioblastoma; DC-ATA=dendritic cells incubated with autologous irradiated tumor cells or with a lysate of autologous tumor antigens from irradiated tumor cells, TC=tumor cells, MC= monocytes. AE=adverse event. SAE=severe adverse event, and RX=treatment.

Table 3. Numbers of DC-ATA products injected by clinical trial. Numbers reported are the average numbers of cells injected during each of the first three injections.

Trial	# patients	Median # cells injected x 10^Citation6	Mean # cells injected x 10^Citation6 ± standard deviation	Lowest # cells injected x 10^Citation6	Highest # cells injected x 10^Citation6
Renal Cell	9	12.8	14.9 ± 7.4	6.0	28.2
Melanoma	54	15.0	15.4 ± 6.4	4.8	33.1
Melanoma	18	13.0	12.5 ± 3.7	5.7	19.1
Hepatoma	8	6.6	8.6 ± 4.5	4.4	16.0
Ovary	28	7.0	10.7 ± 9.0	0.52	29.0
GBM	57	8.5	10.3 ± 7.8	0.27	27.0

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