Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients

Figures & data

Table 1. Patient demographics (n = 13)

Characteristics	Patients N
Median age, years	69
Range	46–81
Gender
Female	2
Male	11
ECOG Performance Status
0	10
1	3
Histology
Epithelial	11
Biphasic	1
Sarcomatoid	1
Baseline SMRP level (ng/mL)
Median	2.9
Range	0.9–36
Therapy after receiving GC1008
Pemetrexed	7
Gemcitabine	4
Vinorelbine	1
Cisplatin/carboplatin	7
Radiation	1
PI3Kinase Inhibitor	1
None	4

Abbreviations: ECOG, Eastern Cooperative Oncology Group; SMRP, serum mesothelin reactive protein

Figure 1. Overall survival of GC1008-treated malignant pleural mesothelioma patients. Kaplan-Meier plot of overall survival for 13 patients with malignant pleural mesothelioma (with 95% confidence limits, dotted lines). Median overall survival was 12 mo.

Figure 2. Plasma levels of TGFβ. Plasma transforming growth factor β (TGFβ) levels as detected by ELISA are plotted vs. time after the initiation of GC1008-based immunotherapy for 8 malignant pleural mesothelioma patients.

Figure 3. Antitumor humoral immune responses. Extracts from four different mesothelioma cell lines were separated by PAGE, transferred to nitrocellulose, and immunoblotted with diluted (1:1500) sera obtained from two malignant pleural mesothelioma patients (1–03 and 1–04) before and 6-weeks after the initiation of GC1008-based immunotherapy. Black boxes highlight increase reactivity as observed in samples obtained in the course of GC1008-based immunotherapy.

Figure 4. Relationship between overall survival and the generation of tumor-targeting antibodies. The overall survival (in months) of 5 malignant pleural mesothelioma (MPM) patients who formed antitumor antibodies in response to GC1008-based is compared with that of 8 MPM patients who failed to do so. Data were compared with a Log-rank test, p value is indicated.

Table 2. Phenotypic characterization of immune cell subsets by cytofluorometric analysis.

NK cell activating receptors (% of NK cells)	Controls (median)	Mesothelioma patients at baseline (median)	P value control vs mesothelioma patients at baseline*	Mesothelioma patients after 1 cycle of GC1008 (median)	P value mesothelioma patients baseline vs treated**
NKG2D	51.5%	58.2%	NS (p = 0.474)	59.9%	NS (p = 0.984)
NKp30	8.5%	2.7%	0.02	2.4%	NS (p = 0.078)
2B4	36.6%	16.1%	0.003	10.1%	0.02
DNAM1	97.7%	96.6%	NS (p = 0.72)	93.2%	0.02
NK cell inhibitory receptors (% of NK cells)
CD94/NKG2A	24.1%	22.1%	NS (p = 0.617)	20.9%	NS (p = 1.00)
CD8^+ T cell activation/negative immunoregulation markers (% of CD8^+ T cells)
PD-1	5.8%	4.2%	0.04	3.8%	NS (p = 0.492)
CD38	34.6%	43.2%	NS (p = 0.143)	50.9%	NS (p = 0.556)
NKG2D	72%	52.5%	0.02	52.9%	NS (p = 0.130)
CD4^+ T cell activation/negative immunoregulation markers (% of CD4^+ T cells)
PD-1	4.0%	5.3%	NS (p = 0.154)	5.0%	NS (p = 0.845)
CD38	17.2%	35%	0.03	40.2	NS (p = 0.375)
NKG2D	0.3%	1.8%	0.005	2.0%	NS (p = 0.976)
T regulatory Cells (CD4^+/FoxP3^+) (% of CD4^+ T cells)	8.7%	4.8%	0.001	4.6%	NS (p = 0.556)

* Abbreviations: NS, not significant; PD-1, programmed cell death 1. *Two sample Mann-Whitney test, **paired Wilcoxon test.