CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients

Gordon, Alan N.; Schultes, Birgit C.; Gallion, B. Holly; Edwards, Robert P.; Whiteside, Theresa L.; Cermák, J; Nicodemus, Christopher F.

doi:10.1016/j.ygyno.2004.04.024

Cited by 79 publications

(42 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…(a) We agree that published studies indicate that oregovomab is capable of inducing CA125-specific immune responses via the idiotypic network and cross-presentation (2,3). We were attempting to provide contrasts between passive immunity provided by traditional antibody approaches and those capable of provoking antigen-specific CTL and T-helper cell responses as well as antibodies.…”

supporting

confidence: 52%

Reply to the Letter to the Editor from Schultes et al

Sabbatini¹,

Odunsi²

2007

Clinical Cancer Research

View full text Add to dashboard Cite

In Response: We wish to thank Drs. Schultes, Smith, and Nicodemus for their questions about our characterization of oregovomab as passive immunotherapy, the potential interference of human anti-mouse antibody (HAMA) in the Luminex assay used in our studies, and clarification on the induction of CA125-specific B-and T-cell responses (1).(a) We agree that published studies indicate that oregovomab is capable of inducing CA125-specific immune responses via the idiotypic network and cross-presentation (2, 3). We were attempting to provide contrasts between passive immunity provided by traditional antibody approaches and those capable of provoking antigen-specific CTL and T-helper cell responses as well as antibodies. They correctly state that both oregovomab and abagovomab should be considered in the latter group.(b) Regarding the possible influence of HAMA on the antihuman cytokine Luminex beads, there is no direct experimental evidence either way. In our study, we found that samples with high HAMA and low HAMA gave the same order of increase in IFN-g, suggesting that the cytokine data are unlikely to be due to HAMA artifact.(c) We agree with our colleagues that Ab3 responses should not be equated with anti-CA125 antibody induction. As they have noted with oregovomab, other studies of abagovomab have reported that a significant proportion of Ab3 antibodies do not bind to the original antigen. Ab1 ¶ antibodies (CA125 specific) were found in only 54% of patients in the study by Pfisterer et al. (4) and in 50.4% of patients in the prior study by Reinertz et al. (5). Interestingly, in the latter study, the association between immune variables and survival showed a consistent survival advantage of the Ab3 responder over the nonresponder, suggesting that the Ab3 response could be considered as a surrogate for clinical vaccine ''activity.'' In fact, patients with a positive HAMA, Ab1 ¶, or antibody-dependent cell cytotoxic response all had a longer median overall survival when compared with those nonresponders in each group. Whereas further analysis of the antibody response and its specificity is important in learning to optimize this vaccine approach, we opted to consider the Ab3 titer as the primary immune study end point with the intention of proceeding to a phase III trial if the construct was immunogenic based on Ab3 titers coupled with an acceptable safety profile. In our study, we showed Ab1 ¶ activity in 3 of 30 patients with posttreatment samples available for testing.(d) We agree that it would be informative if the responses were shown separately for ACA125-(antibody) and CA125-(antigen) specific components of our in vitro stimulation assay. However, we only carried out in vitro stimulation in the presence of sequentially added ACA125 and CA125. We did not dissect out the specific components responsible for our observations. This experimental design was based on the notion that both ACA125 and CA125 are likely to be circulating in the ovarian tumor -bearing host, and the results would more likely reflect the in ...

show abstract

supporting

confidence: 52%

Reply to the Letter to the Editor from Schultes et al

Sabbatini¹,

Odunsi²

2007

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…49 Oregovomab (B43.13, OvaRex) is a monoclonal antibody to CA125 which has been examined in ovarian cancer patients in both phase II and III trials. 49,50 In a prospective, open-label, pilot phase II trial involving heavily pretreated patients with ovarian cancer, antibody and T cell responses specific to both oregovomab and CA125 were generated in the majority of patients. 49 In three patients, these immune responses corresponded to stabilization of disease with survival greater than 2 y.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

“…In a subsequent trial of 20 women with advanced recurrent ovarian cancer, oregovomab was administered alone and then with optionally concurrent second-line chemotherapy. 50 Treatment-induced antibodies were generated, including human anti-mouse antibodies (HAMAs) and anti-oregovomab antibodies (Ab2) in 79% of patients and anti-CA125 antibodies in 11% of patients. T cell responses to CA125, generated in 39% of patients, and to autologous tumor (63% of patients) were significantly associated with improved survival (p = 0.002).…”

Section: Cancer Immunotherapymentioning

confidence: 99%

Immunotherapy in ovarian cancer

Mantia‐Smaldone

Corr

Chu

2012

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

“…Thereby, producing anti-mouse specific antibodies, anti-idiotype antibodies, and antibodies specific to CA-125, inducing a humoral response to CA-125. A phase II clinical trial with 20 recurrent OVCA patients has evaluated the clinical value of the combination of ovregovomab with citotoxic chemotherapy (Gordon et al, 2004). Patients who have received the combined therapy have shown a good tolerance, presenting only mild side effects.…”

mentioning

confidence: 99%

Breast and Ovarian Cancer Treatment: Facing Forward Women's Health Care

Herlinger¹,

Madeira²,

Daltoé³

et al. 2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

View full text Add to dashboard Cite

parameters guide tumor treatment decisions, as well as the disease prognosis evaluation (Arnone et al., 2010). It is likely that BC classification may require revision, as a recent cDNA microarray gene expression profiling study has classified BC into 5 distinct subtypes based on variations in gene expression patterns (Haupt, 2010). These 5 subtypes are luminal A and luminal B, normal breastlike, HER2 overexpressing, and basal-like subtypes (Nielsenet al., 2004;Haupt et al., 2010). BC treatment commonly follows combinatory schemes comprising surgery, radiotherapy, chemotherapy, and/or hormonotherapy. Surgical strategies of breast tumors vary according to the extent of the disease, which is evaluated as in situ carcinoma or invasive cancer. Lobular and ductal in situ carcinomas are treated, respectively, with excisional biopsy then prophylactic use of tamoxifen, or another hormonotherapy approach, for five years (depending on the tumor ER status), and mastectomy followed by radiotherapy. Partial mastectomy may also be considered. Although the discussion of BC surgery is beyond the scope of the present work, it is worthwhile to point that the decision to pursue with mastectomy, partial or radical, must consider that its curative benefit overpasses its mutilation impact on women's psychological health (Barros et al., 2009). On the other hand, invasive BC carcinomas are differentially treated depending on the tumor size, free surgical margins and residual post-surgical disease, skin damage, and the existence of metastasis. When BC is diagnosed as a tumor of 3 cm or less with free surgical margins, the recommendation is conservatory surgery, characterized by segmentar resection, followed by radiotherapy (Veronesi et al., 1995). Axillary linfadenectomy dissection is also advised whenever sentinel lymph node (SLN) tests positive for malignancy, as it indicates lymphoid drainage of the primary tumor micrometastasis (Fisher et al., 1997a). Nonetheless, invasive BC carcinomas larger than 3 cm at the disease diagnosis, both mastectomy and linfadenectomy are indicated. Breast reconstitution may be considered for patients presenting good clinical conditions (Barros et al., 2009). Regarding the conventional pharmacologic control of BC, there are several multidrug regimens preconized for neoadjuvant, adjuvant, or palliative chemotherapy approaches. As for any other antineoplastic approach, BC chemotherapy combines drugs with distinct cytotoxic mechanisms of action aiming the avoidance of drug resistant phenotype development by cancer cells. In this context, current BC chemotherapy schemes include drugs classified as anthracyclines, alkaloid taxanes, nitrogen mustard alkylating agents, antimetabolic drugs, and hormonotherapeutic agents. Of interest, the relevant pharmacodynamic aspects of the cited drugs will be briefly addressed [Drugs mechanisms of action have been reviewed by Brunton (2010)]. Anthracyclines, which include doxorubicin and epirrubicin, are considered cytotoxic antibiotics that comprise a tetracycline ring cou...

show abstract

CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients

Cited by 79 publications

References 24 publications

Reply to the Letter to the Editor from Schultes et al

Reply to the Letter to the Editor from Schultes et al

Immunotherapy in ovarian cancer

Breast and Ovarian Cancer Treatment: Facing Forward Women's Health Care

Contact Info

Product

Resources

About