Clinical and Immune Responses in Resected Colon Cancer Patients Treated With Anti-Idiotype Monoclonal Antibody Vaccine That Mimics the Carcinoembryonic Antigen

Foon, Kenneth A.; John, William J.; Chakraborty, Mala; Das, Ruma; Teitelbaum, April; Garrison, Juanita; Kashala, Oscar; Chatterjee, S. K.; Bhattacharya‐Chatterjee, Malaya

doi:10.1200/jco.1999.17.9.2889

Cited by 155 publications

(82 citation statements)

References 11 publications

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“…The characteristic of generating Ab3 Abs that share idiotopes with P3 mAb (Ab1) has been a common feature observed in mice (18), rabbits, and monkeys immunized with 1E10 mAb (our unpublished observation). The capacity to induce this kind of Ab3 has also been reported by other groups using different anti-Id mAbs (41)(42)(43)(44), indicating the capacity of anti-Id mAbs to generate "true" Ab3 Abs (Ab3, Idϩ).…”

Section: Figuresupporting

confidence: 67%

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

Alfonso

Diaz

Hernández

et al. 2002

The Journal of Immunology

112

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We generated the 1E10 γ-type anti-idiotype mAb (Ab2) specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with Ags expressed on human melanoma and breast carcinoma cells. This Ab2 mAb induced an Ab response in animal models sharing immunochemically defined idiotopes with the Ab1. The treatment of tumor-bearing mice with 1E10 mAb induced a strong antitumor activity. A clinical trial was conducted in 20 patients with advanced malignant melanoma. Patients were treated with six intradermal injections of aluminum hydroxide-precipitated 1E10 anti-Id mAb given at 2-wk intervals. Sixteen of the 17 patients who received at least four doses of the anti-Id vaccine develop Ab3 Abs capable of inhibiting Ab2 binding to Ab1 (Ab3Id+). In contrast to the incapacity of 1E10 mAb to generate Ab3 Abs with the same antigenic specificity as the Ab1 mAb in mice, a very specific and strong Ab3 response against N-glycolyl-containing gangliosides was induced in 16 patients (Ab3Ag+). No evidence of serious or unexpected adverse effects has been observed in this clinical trial. 1E10 anti-Id vaccine was safe, well tolerated, and immunologically effective, with most patients being able to generate a specific immune response against 1E10 and Neu-glycolyl-GM3 ganglioside.

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Section: Figuresupporting

confidence: 67%

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

Alfonso

Diaz

Hernández

et al. 2002

The Journal of Immunology

112

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“…35 Recently, anticancer vaccines based on colon TAA were generated. 35,36 The effectiveness of the vaccines against colon cancer proves the involvement of TAA in the process of immune response induction. Nevertheless, the attempts of the immune system to prevent the development of an antigenic neoplastic disease may be ineffective due to a weak and/or delayed immune reaction, which is overwhelmed by the speed of tumor proliferation and spread.…”

Section: Discussionmentioning

confidence: 99%

Involvement of the immune response in the cure of metastatic murine CT‐26 colon carcinoma by low electric field‐enhanced chemotherapy

Plotnikov

Tichler

Korenstein

et al. 2005

Intl Journal of Cancer

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Low electric field cancer treatment-enhanced chemotherapy (LEFCT-EC) is a new treatment modality that combines chemotherapeutic agents and low electric field stimulation. LEFCT-EC was found to destroy malignant mouse tumors and cause massive death of tumor cells. This may enable the immune system cells to efficiently recognize and eliminate tumor cells at the primary tumor site and at metastatic foci. Mice with 15 mm diameter intracutaneous colon carcinomas (CT-26) were injected with BCNU (35 mg/kg), and 2 min later the tumors were exposed to low electric fields (intensity 40 V/cm, pulse duration 180 s, frequency 500 Hz) for 12 min (LEFCT-EC). We found that treatment with LEFCT-EC achieved complete cure of 93% of the animals. In comparison, electric fields alone (13% cure), chemotherapy alone (0%), surgery (15%) or a combination of surgery and bischloroethyl-nitrosurea, carmustine (BCNU; 84%) treatments resulted in lower cure rates. After treatment and cure with LEFCT-EC, 50% of the cured mice developed resistance to a tumor challenge (surgery 1 BCNU only 15%). Furthermore, splenocytes from cured animals protected naive animals from a tumorigenic dose of tumor cells. Separation of spleen cells into lymphocyte subpopulations indicated a major role for CD4 and CD8 T cells in this protection. FACS analysis revealed restoration of normal splenocyte subpopulation proportions impaired by cytotoxic chemotherapy. Our results suggest that LEFCT-EC can directly destroy primary tumors and facilitate the destruction of metastatic disease by enforcement of antitumor immune responses. ' 2005 Wiley-Liss, Inc.Key words: electrostimulation; metastases; colon cancer; chemotherapy; antitumor immune response About 11% of all new cancer cases in the USA in 2004 are colorectal cancer (CRC), making it the third most common malignancy in both sexes in developed countries. 1 Surgical resection remains the primary treatment modality for localized disease with a relapse-free rate of approx. 50%. 2 Although 15-20% of initially diagnosed patients with CRC have distant metastases, most patients develop metastasis at some point during the disease cycle, and the 5-year survival rate with metastasis has been reported as <5%. 3 We report here a recently developed method for the treatment of metastatic malignancies, which takes advantage of the specific synergistic effects of low electric fields and chemotherapy. This approach is based on the phenomenon of electrically enhanced endocytosis (electroendocytosis) of macromolecules (molecular weight of 1-2,000 kD) after exposure of cells to low unipolarpulsed electric fields (2.5-80V/cm). [4][5][6] It should be stressed that this process differs fundamentally from that of electroporation. Electroporation, which was initially discovered more than 2 decades ago, is characterized by induction of very short-lived (in the microsecond time domain) permeability changes in the plasma membrane by high electric fields (250-5,000 V/cm). The typical exposure to fields inducing electroporation consists of a sing...

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“…Finally, it has to be noted that the encouraging preliminary results from independent pilot studies on patients with respectively advanced (Foon et al, 1997) and resected (Foon et al, 1999) colorectal cancer treated with an anti-Id mAb that is the internal image of CEA still await further confirmation. In those trials, most patients developed both anti-anti-Id polyclonal antibodies and cellular immune responses specific for both the anti-Id used for treatment and the actual CEA expressed by the tumor of the patients.…”

Section: Colorectal Cancermentioning

confidence: 99%

Anti-idiotype antibodies in cancer treatment

et al. 2007

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As a cancer immunotherapy tool, idiotypes (Ids) have been used in different ways over the last three decades, depending on the actual human tumor cell target. It all started with passive, monoclonal, anti-Id antibody treatment of B-cell lymphoma, a setting in which results were tantalizing, but logistics unsustainable. It then moved toward the development of anti-Id vaccines for the treatment of the same tumors, a setting in which we have recently provided the first formal proof of principle of clinical benefit associated with the use of a human cancer vaccine. Meanwhile, it also expanded in the direction of exploiting the antigenic mimicry of some Ids with Idunrelated, tumor-associated antigens for the immunotherapy of a number of solid tumors, a setting in which clinical results are still far from being consolidated. All in all, over the years Id-based immunotherapy has paved the way for a number of seminal therapeutic improvements for cancer patients, including the development of most if not all Id-unrelated monoclonal antibodies that have recently revolutionized the field.

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Clinical and Immune Responses in Resected Colon Cancer Patients Treated With Anti-Idiotype Monoclonal Antibody Vaccine That Mimics the Carcinoembryonic Antigen

Cited by 155 publications

References 11 publications

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

Involvement of the immune response in the cure of metastatic murine CT‐26 colon carcinoma by low electric field‐enhanced chemotherapy

Anti-idiotype antibodies in cancer treatment

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