Delving into the Latest Updates on Recombinant Saccharomyces cerevisiae-CEA(GlobeImmune) with Synapse

Overview

Basic Info

Drug Type

Recombinant vector vaccine, Therapeutic vaccine

Synonyms

Recombinant Saccharomyces cerevisiae-CEA (610D)

Target

CEA

Mechanism

CEA inhibitors(Carcinoembryonic antigen inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [3]

Active Indication-

Inactive Indication

Colorectal CancerHepatocellular CarcinomaMelanoma+ [8]

Originator Organization

GlobeImmune, Inc.

Active Organization-

Inactive Organization

ImmunityBio, Inc.

GlobeImmune, Inc.

NantKwest, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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The 5-year survival rate for stage IB-III non-small-cell lung cancer (NSCLC) remains 15%. Surgical resection followed by adjuvant chemotherapy with cisplatin and vinorelbine is one standard-of-care. We sought to determine in a preclinical model whether (a) the combination of cisplatin and vinorelbine could positively modulate components of the immune system independent of antitumor activity, and (b) there were synergistic effects of this drug combination and vaccine immunotherapy. We examined the effect of cisplatin/vinorelbine on gene expression, cell-surface phenotype, and CTL-mediated cytolysis of murine lung carcinoma cells in vitro; we also assessed the effects of cisplatin/vinorelbine on immune subsets and function of Tregs in vivo. Finally, we evaluated the potential synergy between chemotherapy and a recombinant yeast-CEA vaccine in a murine model transgenic for CEA with mice bearing lung tumors. These studies demonstrate that exposure of lung tumor cells to the platinum doublet cisplatin/vinorelbine modulates tumor cell phenotype and increases sensitivity to CTL-mediated cytolysis. These studies also demonstrate that cisplatin/vinorelbine (a) induces sub-myeloablative leucopenia that differentially modulates reconstitution of Treg versus effector T-cell subsets and (b) can be employed synergistically with vaccine, exploiting homeostatic peripheral expansion of T cells. Antitumor studies show for the first time that cisplatin/vinorelbine combined with vaccine increases the survival of mice with established NSCLC. These findings provide the rationale for the potential clinical benefit of the combined use of vaccine with cisplatin/vinorelbine chemotherapy regimens.

01 Nov 2000·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

The use of a rapid ELISPOT assay to analyze peptide-specific immune responses in carcinoma patients to peptide vs. recombinant poxvirus vaccines

Q2 · MEDICINE

Article

Author: J L Marshall ; A Chen ; P Arlen ; S M Steinberg ; K Y Tsang ; J M Hamilton ; D Poole ; J Schlom ; P H Hand

An enzyme-linked immunosorbent spot (ELISPOT) assay for interferon gamma production has been used to analyze specific T cell responses to a Flu 9-mer peptide, and a 9-mer peptide of carcinoembryonic antigen (CEA). Assays were performed on peripheral blood mononuclear cells (PBMC) of HLA-A2-positive patients with CEA-expressing carcinomas, both before and after vaccination with CEA-based vaccines, and from HLA-A2-positive healthy blood donors. The ELISPOT assay utilized aliquots of frozen PBMC, and assays were performed after 24 h in culture with peptide to rule out any artifacts due to long-term in vitro stimulation cycles. An internal standard was used for each assay to define reproducibility of the assay, and all samples from a given patient (pre- and post-vaccination, with both the Flu and CEA peptides) were analyzed simultaneously. The results indicated a trend towards healthy blood donors having higher levels of Flu-specific T cell precursors than do colon carcinoma patients, but these results were not statistically significant (P = 0.06). On the other hand, slightly higher CEA-specific T cell responses were observed in cancer patients with CEA-expressing carcinomas than in healthy blood donors. PBMC from two CEA-based vaccine clinical trials were analyzed for T cell responses to the same CEA peptide and to the Flu control peptide. The first trial consisted of three monthly vaccinations of CEA peptide (designated PPP) in adjuvant. The second trial consisted of cohorts receiving three monthly vaccinations of avipox-CEA recombinant (designated AAA) or cohorts receiving a primary vaccination with recombinant vaccinia-CEA followed by two monthly vaccinations with avipox-CEA (designated VAA). Few, if any, CEA-specific T cell responses were seen in the PPP vaccinations, while the majority of patients receiving the poxvirus CEA recombinants demonstrated increases in CEA-specific T cell responses and no increases in Flu-specific responses. CEA-specific IgG responses were also demonstrated in patients following recombinant CEA poxvirus vaccinations. Statistical analyses of the T cell responses to the same CEA peptide demonstrated a P value of 0.028 for the recombinant poxvirus vaccines, as compared with the peptide vaccine. There were no differences seen (P = 0.37) in Flu-specific responses after these two types of CEA vaccination. These results thus provide the first evidence that poxvirus recombinant-based vaccines are more potent in the initiation of tumor-antigen-specific T cell responses than vaccines employing peptide in adjuvant, when assays are conducted in an identical manner, and in defining responses to the same peptide. These results also demonstrate for the first time that an ELISPOT assay, performed over a 24-h period and without in vitro sensitization, can be successfully used to monitor immune responses to a tumor-associated antigen in cancer patients.

01 Jan 2000·Clinical cancer research : an official journal of the American Association for Cancer Research

Human autoantibodies to carcinoembryonic antigen (CEA) induced by a vaccinia-CEA vaccine.

Article

Author: Allen, K O ; Lee, S ; Conry, R M ; Moore, S E ; LoBuglio, A F ; Shaw, D R

Carcinoembryonic antigen (CEA) is a well-characterized oncofetal glycoprotein whose overexpression by human adenocarcinomas has been a target for cancer immunotherapy. Limited information is available regarding the ability of patients to mount an antibody response to this self-antigen following vaccination. Recombinant vaccinia viruses encoding full-length or internally deleted cDNAs for human CEA were used to vaccinate 32 patients with CEA-expressing adenocarcinomas, predominantly of colorectal origin. CEA-specific autoantibodies were induced by vaccination in 7 of 32 patients. None of the patients had CEA antibodies detected before vaccination. CEA specificity of the antibodies initially identified by ELISA was confirmed by competitive inhibition analysis as well as recognition of recombinant CEA produced in baculovirus-infected insect cell cultures and human cell cultures by Western blot. The CEA autoantibodies were predominantly IgG1, with a minority of patients also demonstrating IgM autoantibodies. CEA antibodies were of low titer and low avidity, based on competitive inhibition assays. These autoantibodies did not affect clinical serum CEA protein quantitation. Furthermore, elevated serum CEA levels commonly encountered in patients with advanced adenocarcinoma did not hinder detection of low avidity polyclonal CEA antibodies. CEA antibodies such as those induced in these pilot trials are projected to have modest antitumor activity. Thus, additional Phase I/II trials of recombinant vaccinia-CEA with alternative prime-boost approaches and/or augmentation strategies are warranted in an effort to enhance the frequency and avidity of CEA-specific autoantibodies and cytolytic T cells before Phase III trials.

100 Deals associated with Recombinant Saccharomyces cerevisiae-CEA(GlobeImmune)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 2	US	NantKwest, Inc.	25 May 2018
Non-Small Cell Lung Cancer	Phase 2	-	ImmunityBio, Inc.	01 Feb 2018
Squamous Cell Carcinoma	Phase 2	US	NantKwest, Inc.	13 Jan 2018
Melanoma	Phase 2	-	ImmunityBio, Inc.	01 Dec 2017
Squamous Cell Carcinoma of Head and Neck	Phase 2	-	ImmunityBio, Inc.	01 Dec 2017
Transitional Cell Carcinoma	Phase 2	-	ImmunityBio, Inc.	01 Dec 2017
Triple Negative Breast Cancer	Phase 2	-	ImmunityBio, Inc.	01 Dec 2017
Triple Negative Breast Cancer	Phase 2	-	ImmunityBio, Inc.	01 Dec 2017
Thyroid Cancer	Phase 2	US	GlobeImmune, Inc.	26 Apr 2013
Thyroid Cancer, Medullary	Phase 2	US	ImmunityBio, Inc.	26 Mar 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03586869 (QUILT-3.080, CTgov)	Phase 1/2	Pancreatic Cancer	3	Avelumab+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+ETBX-011+fluorouracil+ALT-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+haNK for infusion+Leucovorin+GI-6207+bevacizumab+Oxaliplatin+Capecitabine	wgevgjuiph(ezpqcgkztp) = tkqivopnnq zmjhywxaus (bbzddafkcc, jxttebkpjd - yscykclxja) View more	-	27 Aug 2024
NCT03387085 (QUILT-3.067, CTgov)	Phase 1/2	Triple Negative Breast Cancer	9	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+ETBX-011+5-fluorouracil+N-803+nab-paclitaxel+CYCLOPHOSPHAMIDE+Avelumab+haNK for Infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	dvirbbfggx(fitzpwwuwp) = mpdvbnlfea pxtfftzzto (ffkjooidky, bwyevgsujr - yxawvupuhv) View more	-	09 Aug 2024
NCT03387111 (CTgov)	Phase 1/2	Squamous Cell Carcinoma	4	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+cetuximab+ETBX-061+ETBX-051+ETBX-011+Necitumumab+fluorouracil+N-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+Avelumab+haNK for infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	wmktykeske(juyhknjpfb) = cvascevwou rnkywbusjd (zyasrzjfzm, exyiviepfs - utukadsyqw) View more	-	05 Aug 2024
NCT01856920 (QUILT-3.006, CTgov)	Phase 2	Thyroid Cancer, Medullary	35	GI-6207 (Surveillance Subjects)	xkpimuodex(stwsffgoth) = aftwhsfeub rtybxyxbzv (tudxprhfll, ulbascyceg - ojymunhorc) View more	-	09 Jul 2024
NCT01856920 (QUILT-3.006, CTgov)	Phase 2	Thyroid Cancer, Medullary	35	CEA (610D)+GI-6207 (Vaccine Subjects)	xkpimuodex(stwsffgoth) = rheeccrvip rtybxyxbzv (tudxprhfll, igoukpfvfn - aifjokgzto) View more	-	09 Jul 2024