Induction of delayed-type hypersensitivity responses by monoclonal anti-idiotypic antibodies to tumor cells expressing carcinoembryonic antigen and tumor-associated glycoprotein-72

Irvine, Kari R.; Schlom, Jeffrey

doi:10.1007/bf01741166

Cited by 12 publications

(6 citation statements)

References 36 publications

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“…Such Ab2 preparations may have high potential of eliciting specific humoral immunity in cancer patients. Like monoclonal Ab2 FG1 described here, a few of those Ab2s also elicited specific DTH reactions after challenge with antigen-positive tumor cells in experimental animals (Austin et al, 1991;Chen et al, 1991;Pohl et al, 1992;Irvine and Schlom, 1993;Mansoor et al, 1993). However, in each of those studies, human tumor cells expressing the relevant antigen were used for challenge.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal anti-idiotypic antibody functionally mimics the human gastrointestinal carcinoma epitope GA733

Maruyama

Benden

et al. 1996

Int. J. Cancer

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Anti-idiotypic antibodies (Ab2) that bind to the antigencombining region of anti-tumor antibodies (Ab I) may functionally, and even structurally, mimic tumor antigen. We have previously demonstrated that polyclonal goat Ab2 directed against anti-human gastrointestinal carcinoma Ab I GA733 induces anti-anti-idiotypic antibodies (Ab3) in animals that are Ab I -like in their binding specificity and idiotope expression. To obtain more defined Ab2 vaccines with potentially increased specificity and efficacy, a monoclonal Ab2 (FG I) was produced against Ab I GA733 in rats. The monoclonal Ab2 FG I, similar to the polyclonal Ab2 described previously, induced Ab3 in rabbits that were Ab I -like in their idiotope expression and binding specificity to tumor cells and antigen. Antigen-specific Ab3 induced by Ab2 FG I were easily detected in unprocessed rabbit sera, whereas the demonstration of such Ab3 after polyclonal Ab2 immunization required purification of the Ab3 from the rabbit sera. In addition, Ab2 FG I induced antigen-specific humoral and cellular immunity in mice. Murine Ab3 bound specifically to antigen-positive tumor cells. Ab2-immunized mice showed antigen-specific delayed-type hypersensitivity (DTH) reaction, and cultured splenocytes from the immune mice demonstrated specific proliferation and cytokine (interferon-y and interleukin-4) secretion upon stimulation with GA733 antigen. However, immune mice were not protected against a challenge with syngeneic GA733 antigen-expressing colon carcinoma cells.o 1996 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Monoclonal anti-idiotypic antibody functionally mimics the human gastrointestinal carcinoma epitope GA733

Maruyama

Benden

et al. 1996

Int. J. Cancer

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“…T cell immunity against anti-id MAbs against anti-CEA MAbs have also been re ported [4,12,14]. Durrant et al [4] demon strated that tumor-infiltrating lymphocytes obtained from colon cancer patients and stim ulated in vitro with anti-id MAbs proliferated in response to purified CEA.…”

Section: Application Of Anti-id Mab For Tumor Immunotherapymentioning

confidence: 99%

“…How ever, Irvine and Schlom [12] have recently reported that anti-id MAb against anti-carbo hydrate antigen TAG72 MAb could induce a DTH response in BALB/c mice. MacLean et al [13] have observed a DTH reaction at the subcutaneous vaccination site to the synthetic form of the immunodominant disaccharide ((3-Gal-3 GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH in patients with ovarian cancer.…”

Section: Application Of Anti-id Mab For Tumor Immunotherapymentioning

confidence: 99%

“…Durrant et al [4] demon strated that tumor-infiltrating lymphocytes obtained from colon cancer patients and stim ulated in vitro with anti-id MAbs proliferated in response to purified CEA. Irvine and Schlom [12] have shown that immunization of mice with an anti-id MAb against anti-CEA MAb COL-1 could induce specific DTH cell-mediated immune responses to murine tumor cells that express human CEA on their surface. In addition, their group [14] [16,17].…”

Section: Application Of Anti-id Mab For Tumor Immunotherapymentioning

confidence: 99%

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Internal Image-Bearing Anti-ldiotypic Monoclonal Antibodies

et al. 1995

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Five anti-idiotypic (Id) monoclonal antibodies (MAbs) (Ab2) were prepared from a BALB/c mouse immunized with anti-carcinoembryonic antigen (CEA) MAb MA208 (Ab1) in a syngeneic system. These anti-Id MAbs appear to recognize unique idiotopes at the combining site of MAb MA208, because they were specifically reactive with MAb MA208 and showed inhibitory activity against the binding of MAb MA208 to CEA. These MAbs were divided into three groups according to the analysis of anti-anti-Id antibodies (Ab3) induced with each anti-Id MAb. Anti-anti-Id MAb M7–625 antiserum (Ab3) reacted with purified CEA in a binding assay and in Western blot analysis, and competed with Ab1 binding to CEA. Furthermore, the binding of anti-Id MAb M7–625 to MAb MA208 was inhibited with CEA, indicating that Ab2 mimics the structure of the epitope in CEA which was recognized with Ab1. These serologic findings suggest that anti-Id MAb M7–625 carries the internal image of the antigen. According to the amino acid sequences of complementarity determining region (CDR) 1, 2 and 3 of the MAb M7–625 variable region, homology of amino acid sequences exists between CDR2 in the H chain (5 amino acids of 10) and domain III of CEA (545–554). Seven anti-Id MAbs were then generated using anti-CEA synthetic peptide MAb P1-356 to analyze further the epitope structure of CEA. These anti-Id MAbs were divided into four groups. Serological analyses as described above suggested that among them, anti-Id MAb M315 had an internal image. We therefore prepared anti-anti-Id MAbs using anti-Id MAb M315. Among them, anti-anti-Id MAb 11B2 reacted directly with CEA and competed with MAb P1–356 in the competition assay. In addition, MAb 11B2 stained both cultured CEA-producing cells and colonic cancer tissues, suggesting that MAb 11B2 is Abl like Ab3. These MAbs (Ab1-3) will be of use for the structural analysis of the internal image.

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“…Whereas an Ab2P generated against an anti-CEA monoclonal antibody that recognizes a CEA-specific epitope, would be theoretically safer and more effective. Furthermore, Ab2fl expressed in a different molecular environment have been shown to overcome the immunosuppression in the host by stimulating "silent clones," and/or allowing (19)(20)(21)(22)(23)(24)(25)(26)(27). We have generated and characterized an anti-idiotype murine monoclonal antibody to a murine monoclonal antibody designated 8019 that identifies a specific epitope on CEA (28).…”

Section: Introductionmentioning

confidence: 99%

Immune response to the carcinoembryonic antigen in patients treated with an anti-idiotype antibody vaccine.

Foon¹,

Chakraborty²,

John³

et al. 1995

J. Clin. Invest.

115

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We have generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) designated 3H1, which mimics a specific epitope on the carcinoembryonic antigen (CEA). Patients with CEA positive tumors are immunologically "tolerant" to CEA. We used 3H1 as a surrogate for CEA for vaccine therapy of 12 patients with advanced colorectal cancer. Each of the patients received a minimum of four intracutaneous injections of aluminum hydroxide precipitated 3H1 at either 1, 2, or 4 mg dosage per injection. 9 of 12 patients demonstrated anti-anti-idiotypic (Ab3) response to 3H1. All nine patients generated specific anti-CEA antibody demonstrated by reactivity with radiolabeled purified CEA; some cases were confirmed by immunoprecipitation of purified CEA. We also demonstrated Ab3 stained both autologous and allogeneic colonic tumors. 7 of 12 patients demonstrated idiotype specific T cell proliferative responses and four also showed T cell proliferation to CEA. Toxicity was limited to local reaction with mild fever and chills. All 12 patients eventually progressed after finishing 4-13 dosages. This is the first report demonstrating that a vaccine therapy is capable of breaking "immune tolerance" to CEA in patients with CEA positive tumors. Future studies will focus on treating patients with minimal residual disease. (J. Clin. Invest. 1995. 96:334-342

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Induction of delayed-type hypersensitivity responses by monoclonal anti-idiotypic antibodies to tumor cells expressing carcinoembryonic antigen and tumor-associated glycoprotein-72

Cited by 12 publications

References 36 publications

Monoclonal anti-idiotypic antibody functionally mimics the human gastrointestinal carcinoma epitope GA733

Monoclonal anti-idiotypic antibody functionally mimics the human gastrointestinal carcinoma epitope GA733

Internal Image-Bearing Anti-ldiotypic Monoclonal Antibodies

Immune response to the carcinoembryonic antigen in patients treated with an anti-idiotype antibody vaccine.

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