About RecombiMAb anti-mouse PD-1 (CD279) (D265A) The RMP1-14-CP151 monoclonal antibody is a chimeric version of the original RMP1-14 antibody. The variable domain sequences are identical to the original RMP1-14 but the constant region sequences have been switched from rat IgG2a to mouse IgG2a. The RMP1-14-CP151 antibody also contains a D265A mutation in the Fc fragment rendering it unable to bind to endogenous Fcγ receptors. RMP1-14-CP151 reacts with mouse PD-1 (programmed death-1) also known as CD279. PD-1 is a 50-55 kDa cell surface receptor encoded by the Pdcd1 gene that belongs to the CD28 family of the Ig superfamily. PD-1 is transiently expressed on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. PD-1 expression declines after successful elimination of antigen. Additionally, Pdcd1 mRNA is expressed in developing B lymphocytes during the pro-B-cell stage. PD-1’s structure includes a ITIM (immunoreceptor tyrosine-based inhibitory motif) suggesting that PD-1 negatively regulates TCR signals. PD-1 signals via binding its two ligands, PD-L1 and PD-L2 both members of the B7 family. Upon ligand binding, PD-1 signaling inhibits T-cell activation, leading to reduced proliferation, cytokine production, and T-cell death. Additionally, PD-1 is known to play key roles in peripheral tolerance and prevention of autoimmune disease in mice as PD-1 knockout animals show dilated cardiomyopathy, splenomegaly, and loss of peripheral tolerance. Induced PD-L1 expression is common in many tumors including squamous cell carcinoma, colon adenocarcinoma, and breast adenocarcinoma. PD-L1 overexpression results in increased resistance of tumor cells to CD8 T cell mediated lysis. In mouse models of melanoma, tumor growth can be transiently arrested via treatment with antibodies which block the interaction between PD-L1 and its receptor PD-1. For these reasons anti-PD-1 mediated immunotherapies are currently being explored as cancer treatments. RecombiMAb anti-mouse PD-1 (CD279) (D265A) Specifications IsotypeMouse IgG2a, κ Recommended Isotype Control(s)RecombiMAb mouse IgG2a (D265A) isotype control, anti-hen egg lysozyme Recommended Dilution BufferInVivoPure pH 7.0 Dilution Buffer ImmunogenSyrian Hamster BKH cells transfected with mouse PD-1 cDNA Reported Applicationsin vivo blocking of PD-1/PD-L signaling FormulationPBS, pH 7.0 Contains no stabilizers or preservatives Endotoxin≤0.5EU/mg (≤0.0005EU/μg)Determined by LAL gel clotting assay Aggregation<5% Determined by SEC Purity≥95%Determined by SDS-PAGE Sterility0.2 μm filtration ProductionPurified from CHO cell supernatant in an animal-free facility PurificationProtein G RRIDAB_2927525 Molecular Weight150 kDa StorageThe antibody solution should be stored at the stock concentration at 4°C. Do not freeze. Application ReferencesRecombiMAb anti-mouse PD-1 (CD279) (D265A) (CLONE: RMP1-14-CP151)Maldonado MDM, Gracia-Hernandez M, Le LH, Iida M, Gulley JL, Donahue RN, Palena C, Schlom J, Hamilton DH (2025). "Combination of a therapeutic cancer vaccine targeting the endogenous retroviral envelope protein ERVMER34-1 with immune-oncology agents facilitates expansion of neoepitope-specific T cells and promotes tumor control" J Immunother Cancer 13(5):e011378. PubMedBackground: Endogenous retroviruses (ERVs) are remnants of retrovirus germline infections that occurred over the course of evolution and constitute between 5% and 8% of the human genome. While ERVs tend to be epigenetically silenced in normal adult human tissues, they are often overexpressed in carcinomas and may represent novel immunotherapeutic targets. This study characterizes the ERV envelope protein ERVMER34-1 as a target for a therapeutic cancer vaccine. Methods: The expression of ERVMER34-1 in multiple healthy adult and cancer tissues was assessed, as was its immunogenicity, to ascertain whether specific T cells could lyse human carcinoma cell lines expressing ERVMER34-1. Furthermore, the ability of a rationally designed ERVMER34-1-targeted therapeutic vaccine to induce tumor clearance in two murine carcinoma models expressing ERVMER34-1 was examined either as a monotherapy or in combination with anti-programmed cell death protein-1/programmed death-ligand 1 monoclonal antibody (mAb) or the interleukin-15 superagonist N-803. Results: The ERVMER34-1 protein was shown to be overexpressed in 232/376 of human carcinomas analyzed while being absent in most healthy adult tissues. High levels of ERVMER34-1 RNA expression associate with decreased survival in uveal melanoma, adenoid cystic, and head and neck carcinomas. ERVMER34-1-specific T cells were detected in peripheral blood mononuclear cells (PBMCs) of patients with cancer but not healthy donors following an overnight stimulation. However, reactive T cells are readily expanded from both healthy donor and patient with cancer PBMCs following a 7- day in vitro stimulation. Furthermore, ERVMER34-1-specific T cells selectively kill human carcinoma cell lines expressing ERVMER34-1. A novel, rationally designed, therapeutic cancer vaccine targeting ERVMER34-1 mediated tumor control in established syngeneic murine tumors expressing the full-length ERVMER34-1 protein. When combined with checkpoint blockade, the vaccine promoted expansion of neoepitope-reactive T cells whose function was further enhanced when combined with N-803. This expansion of neoepitope-reactive T cells was associated with tumor control. Conclusions: This study reveals the potential of a vaccine that targets the retroviral envelope protein ERVMER34-1 and supports its continued development toward clinical testing as a new class of therapeutic cancer vaccine.Lepland A, Peranzoni E, Haljasorg U, Asciutto EK, Crespí-Amer M, Modesti L, Kilk K, Lombardia M, Acosta G, Royo M, Peterson P, Marigo I, Teesalu T, Scodeller P (2025). "Peptide-Drug Conjugate for Therapeutic Reprogramming of Tumor-Associated Macrophages in Breast Cancer" Adv Sci (Weinh) 12(10):e2410288. PubMedIn triple-negative breast cancer (TNBC), pro-tumoral macrophages promote metastasis and suppress the immune response. To target these cells, a previously identified CD206 (mannose receptor)-binding peptide, mUNO was engineered to enhance its affinity and proteolytic stability. The new rationally designed peptide, MACTIDE, includes a trypsin inhibitor loop, from the Sunflower Trypsin Inhibitor-I. Binding studies to recombinant CD206 revealed a 15-fold lower KD for MACTIDE compared to parental mUNO. Mass spectrometry further demonstrated a 5-fold increase in MACTIDE's half-life in tumor lysates compared to mUNO. Homing studies in TNBC-bearing mice shows that fluorescein (FAM)-MACTIDE precisely targeted CD206+ tumor-associated macrophages (TAM) upon intravenous, intraperitoneal, and even oral administration, with minimal liver accumulation. MACTIDE was conjugated to Verteporfin, an FDA-approved photosensitizer and YAP/TAZ pathway inhibitor to create the conjugate MACTIDE-V. In the orthotopic 4T1 TNBC mouse model, non-irradiated MACTIDE-V-treated mice exhibited anti-tumoral effects comparable to those treated with irradiated MACTIDE-V, with fewer signs of toxicity, prompting further investigation into the laser-independent activity of the conjugate. In vitro studies using bone marrow-derived mouse macrophages showed that MACTIDE-V excluded YAP from the nucleus, increased phagocytic activity, and upregulated several genes associated with cytotoxic anti-tumoral macrophages. In mouse models of TNBC, MACTIDE-V slowed primary tumor growth, suppressed lung metastases, and increased markers of phagocytosis and antigen presentation in TAM and monocytes, increasing the tumor infiltration of several lymphocyte subsets. MACTIDE-V is proposed as a promising peptide-drug conjugate for modulating macrophage function in breast cancer immunotherapy.Yuan X, Hao X, Chan HL, Zhao N, Pedroza DA, Liu F, Le K, Smith AJ, Calderon SJ, Lieu N, Soth MJ, Jones P, Zhang XH, Rosen JM (2024). "CREB-binding protein/P300 bromodomain inhibition reduces neutrophil accumulation and activates antitumor immunity in triple-negative breast cancer" JCI Insight 9(20):e182621. PubMedTumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB-binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated cytotoxic T cells. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC.
