Immunotherapy for colorectal cancer

Foon, Kenneth A.

doi:10.1007/s11912-001-0010-y

Cited by 14 publications

(9 citation statements)

References 88 publications

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“…Among the treatment strategies to develop an effective immune response against tumor-associated antigens is the use of anti-idiotype (Ab2) MAb as antigen surrogates. [11][12][13][14][15][16][17] The use of Ab2 as vaccines arose as a consequence of Jerne's theory, 18 that postulates the existence of Ab2 that carry the "internal image" of antigenic epitopes.…”

Section: Introductionmentioning

confidence: 99%

1E10 anti-idiotype vaccine in non-small cell lung cancer: Experience in stage IIIb/IV patients.

Alfonso

Díaz²,

Torre³

et al. 2007

Cancer Biology & Therapy

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Conventional treatment of non-small cell lung cancer (NSCLC) has apparently reached a plateau of effectiveness in improving the survival of the patients. For that reason the search for new therapeutic strategies in this type of tumor is justified. 1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to P3 Ab1 MAb, which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some tumors, including those from the lung. We report the treatment with aluminum hydroxide-precipitated 1E10 MAb of 34 stage IIIb and 37 stage IV NSCLC patients. These patients were treated with the anti-idiotype vaccine, after received standard chemotherapy and radiotherapy, in a compassionate-use basis study. Patients received five bi-weekly injections of 1 mg of 1E10/Alum, other 10 doses at 28-day intervals and later the patients who maintained a good performance status continued to be immunized at this same time interval. No evidence of unexpected or serious adverse effects was reported. The median survival time of the 56 patients who entered the study with partial response or disease stabilization and with a PS 1 after the first line of chemo/radiotherapy, was 11.50 months from starting vaccination. In contrast, the median survival time calculated for patients who started vaccination with progressive disease and/or a PS2 was 6.50 months.

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Section: Introductionmentioning

confidence: 99%

1E10 anti-idiotype vaccine in non-small cell lung cancer: Experience in stage IIIb/IV patients.

Alfonso

Díaz²,

Torre³

et al. 2007

Cancer Biology & Therapy

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“…Since tumor antigens are allergerly weakly or tolerizing antigens that have already escaped tumor immune surveillance, the challenge is to present these antigens in a way such as to break the immune surveillance. Autologous tumor cells, either virally modified or admixed with BCG, have shown beneficial clinical effects on patients with colon cancer 3, 4. Since tumor cells are not equipped with the molecular apparatus necessary for proper antigen presentation, the antitumor effect observed in these clinical trials is likely to be mediated by DC.…”

mentioning

confidence: 99%

Influence of drug‐induced apoptotic death on processing and presentation of tumor antigens by dendritic cells

Buttiglieri¹,

Galetto²,

Forno

et al. 2003

Intl Journal of Cancer

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Here we have studied the effects of apoptotic cell death induced by chemotherapic agents on tumor phagocytosis by dendritic cells (DC) and presentation of the relevant antigen to T lymphocytes. Annexin-V-FITC (Ann-V) and propidium iodide (PI) staining was used to assess early apoptotic (Ann-V ؉ /PI ؊ ) vs. late apoptotic/secondary necrotic (Ann-V ؉ /PI ؉ ) death after a 24 hr observation of untreated and drug-treated gastric carcinoma cells. After treatments, the HLA-A*0201 ؉ tumor cell line KATO III was exposed for 24 hr to allogeneic, HLA-related GM-CSF, IL-4-driven immature (i) DC. Tumorloaded iDC were tested for IL-12 release in an ELISA assay, incubated with the DC-maturating factor TNF-␣ and used as stimulators for autologous T lymphocytes. Generation of antitumor T response against KATO cells was evaluated in an anti-MHC class I MAb-blocked Interferon-␥ ELISPOT assay. After treatment with Cis-platin (cis), all dying cells were in early apoptosis, whereas secondary necrosis was the prevalent death pattern observed after epirubicin (epi) and doxorubicin (doxo). Doxo and epi increased tumor expression of heat shock protein (hsp) 70 and uptake of tumor cell components by DC, whereas cis treatment had no effect on hsp70 and was associated with poor tumor uptake by DC. Significant upmodulation of IL-12 was observed by DC that had taken up the doxo-and epi-treated tumors (p< 0.005 and p< 0.01, respectively). Increased IFN-␥ release was also observed after stimulation of T lymphocytes with DC loaded with doxo-and epi-treated (p< 0.02 and p< 0.005, respectively) but not with cis-treated DC. These data show that the products of early apoptosis cannot efficiently cross-activate MHC class I-restricted anti-tumor lymphocytes even in the presence of DC maturating factors, whereas secondary necrosis is associated with robust T cell response.

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“…Vaccination based on tumor antigens seems to be a promising approach for cancer therapy, 31,32) but nevertheless targeting tumor endothelium with endothelial vaccines has many advantages over targeting tumor cells. Firstly, tumor endothelium is a homogeneous population of genetically stable cells with a low probability of losing antigen expression or developing acquired resistance.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity

et al. 2004

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ngiogenesis, the growth of new blood vessels, is essential for tumor growth and metastasis. [1][2][3] In adults, angiogenesis is infrequent due to the balance between inhibitors and stimulators of angiogenesis. But under conditions of hypoxia, tumor cells turn-on the angiogenic switch by secretion of angiogenic stimulators that activate endothelial cells to proliferate and form new blood vessels. 4,5) Proliferation and expression of antigens critical to angiogenesis are two specific characteristics that distinguish angiogenic endothelial cells from quiescent endothelium of normal vasculature. Monoclonal antibodies and synthetic molecules targeting self-angiogenic antigens have been shown to inhibit tumor growth in animal models and were recently used in clinical trials.6-10) However, relatively high doses of these therapeutics have to be administered for long periods of time due to their short biological half-lives. Furthermore, antigens highly specific for angiogenic endothelium still remain to be isolated. These drawbacks should be overcome by active immunization with whole endothelial cells. Recently, active immunization with xenogeneic, but not autologous, endothelial cells was shown to inhibit the growth of experimental tumors in mice.11) However, from the viewpoint of clinical applicability of endothelial vaccines, the use of autologous endothelial cells would be preferable, since xenogeneic immunization may cause a species-specific immune reaction, with undesirable consequences. In the present study, therefore, we aimed to test the usefulness of autologous endothelial vaccine in the treatment of metastatic lesions that are highly dependent on tumor angiogenesis. For this purpose, we immunized BALB/c mice with a vaccine of glutaraldehyde-fixed murine hepatic sinusoidal endothelial cells (HSEs) in a lung metastasis model of colon cancer. We demonstrated that vaccination with autologous HSEs significantly inhibited the development of metastasis through an autoimmune response that was mediated by antibodies and cytotoxic T lymphocytes specifically reactive with endothelial, but not tumor cells. In addition, a vaccine of xenogeneic human umbilical vein endothelial cells (HUVECs) was tested in the same experimental setting, and the effects of both vaccines were compared, both in the animals and in in vitro immunological assays. Materials and MethodsCell culture. Hepatic sinusoidal endothelial cells (HSEs), a cell line isolated from BALB/c mouse, 12) were kindly provided by Dr. Tatsuro Irimura (Faculty of Pharmacology, the University of Tokyo). HSEs were grown in DMEM supplemented with 10% fetal calf serum (FCS) and 1% antibiotic/antimycotic (i.e., 100 U/ml penicillin G, 100 µg/ml streptomycin sulfate, 250 ng/ml amphotericin B; Life Technologies, Grand Island, NY), in an atmosphere containing 5% CO 2 at 37°C. Human umbilical vein endothelial cells (HUVECs) were isolated from fresh umbilical cords (obtained with patients' informed consent, from the Department of Gynecology and Obstetrics, the University of Tokyo)...

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Immunotherapy for colorectal cancer

Cited by 14 publications

References 88 publications

1E10 anti-idiotype vaccine in non-small cell lung cancer: Experience in stage IIIb/IV patients.

1E10 anti-idiotype vaccine in non-small cell lung cancer: Experience in stage IIIb/IV patients.

Influence of drug‐induced apoptotic death on processing and presentation of tumor antigens by dendritic cells

Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity

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