Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer

Wolf, Philipp; Freudenberg, Nikolaus; Bühler, Patrick; Alt, Karen; Schultze-Seemann, Wolfgang; Wetterauer, Ulrich; Elsässer‐Beile, Ursula

doi:10.1002/pros.21090

Cited by 68 publications

(50 citation statements)

References 27 publications

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“…Binding inhibition of the scFv hD7-1(VL-VH) with the parental murine anti-PSMA mAb 3/F11 proved that the scFv retained binding to the same PSMA epitope. No binding inhibition was seen with the anti-PSMA control mAb J591, which is known to bind to a different PSMA epitope ( Figure 2D) (8). Due to its strong and specific PSMA binding, the scFv hD7-1(VL-VH) was identified as a suitable candidate for the construction of the immunotoxins.…”

Section: Resultsmentioning

confidence: 99%

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In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

Michalska

Schultze-Seemann

Kuckuck

et al. 2018

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Section: Resultsmentioning

confidence: 99%

“…The scFv D7 was derived from our murine monoclonal antibody (mAb) to PSMA 3/F11 (8,9). The PE40 domain consists of the structural domains II, Ib and III ( Figure 1).…”

mentioning

confidence: 99%

In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

Michalska

Schultze-Seemann

Kuckuck

et al. 2018

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“…Silver et al (1) and Mhawech-Fauceglia et al (25) found no expression in the parotids. However, PSMA RNA has been found in salivary glands (26), in tissue extracts (27), and by immunohistochemistry (28). A variety of mAbs binding to different epitopes of the extracellular domain of PSMA presented with different stainings of normal tissues (28)-a possible indicator that different splicing variants of PSMA may exist.…”

Section: Discussionmentioning

confidence: 99%

PMPA for Nephroprotection in PSMA-Targeted Radionuclide Therapy of Prostate Cancer

et al. 2015

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Radioactive ligands for the prostate-specific membrane antigen (PSMA) are under development for therapy of metastasized prostate cancer. Since PSMA expression is also found in the kidneys, renal tracer uptake can be dose-limiting. Because kidney kinetics differ from tumor kinetics, serial application of PSMA inhibitors such as 2-(phosphonomethyl)pentanedioic acid (PMPA) may improve the kidney-to-tumor ratio. In this study, we evaluated the effect of PMPA on the biodistribution of 2 promising PSMA ligands. Methods: Human prostate cancer xenografts (LNCaP) were transplanted subcutaneously into mice. After injection of 125 I-MIP1095, a 16-h latency period was allowed for tracer clearance from the blood and renal calices. After baseline scintigraphy, PMPA was injected in doses of 0.2-50 mg/kg (n 5 3 per dose, 5 controls), followed by scans at 2, 4, 6, and 24 h after PMPA injection. Kidney and tumor displacement was determined as a percentage of baseline. A shortened but similar design was used to evaluate the PSMA ligand MIP1404, which contains a chelate for 99m Tc/rhenium. Results: PMPA injection 16 h after MIP1095 translated into a rapid and quantitative relevant displacement of renal activity. Tumor uptake was reduced to a significantly lesser extent in a dose-dependent manner. PMPA doses of 0.2-1 mg/kg appear optimal for sustaining nearly complete tumor uptake while simultaneously achieving near-total blocking of specific renal PSMA binding. The effect was successfully validated with the PSMA ligand MIP1404. Conclusion: PSMA-targeted radionuclide therapy can benefit from serial PMPA comedication by reducing off-target radiation to the kidneys. These data will be used for a first approximation in clinical translation, although in patients an optimization of the dose and time schedule may be necessary.

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“…However, the transferred cells could be only detected at the injection site and not systemically. An optimization of our cell-labeling approach might involve mAb fragments (26,27), which carry fewer radionuclides, and thus induce less damage to their target cells. Furthermore, the missing Fc-part of the mAbs would likely prevent the Fcreceptor-mediated cellular cytotoxicity in vivo, thereby increasing the safety of a possible clinical translation.…”

Section: Discussionmentioning

confidence: 99%

⁶⁴ Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET

Griessinger

Maurer

Kesenheimer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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T cells are key players in inflammation, autoimmune diseases, and immunotherapy. Thus, holistic and noninvasive in vivo characterizations of the temporal distribution and homing dynamics of lymphocytes in mammals are of special interest. Herein, we show that PET-based T-cell labeling facilitates quantitative, highly sensitive, and holistic monitoring of T-cell homing patterns in vivo. We developed a new T-cell receptor (TCR)-specific labeling approach for the intracellular labeling of mouse T cells. We found that continuous TCR plasma membrane turnover and the endocytosis of the specific 64 Cu-monoclonal antibody (mAb)-TCR complex enables a stable labeling of T cells. The TCR-mAb complex was internalized within 24 h, whereas antigen recognition was not impaired. Harmful effects of the label on the viability, DNA-damage and apoptosisnecrosis induction, could be minimized while yielding a high contrast in in vivo PET images. We were able to follow and quantify the specific homing of systemically applied 64 Cu-labeled chicken ovalbumin (cOVA)-TCR transgenic T cells into the pulmonary and perithymic lymph nodes (LNs) of mice with cOVA-induced airway delayedtype hypersensitivity reaction (DTHR) but not into pulmonary and perithymic LNs of naïve control mice or mice diseased from turkey or pheasant OVA-induced DTHR. Our protocol provides consequent advancements in the detection of small accumulations of immune cells in single LNs and specific homing to the sites of inflammation by PET using the internalization of TCR-specific mAbs as a specific label of T cells. Thus, our labeling approach is applicable to other cells with constant membrane receptor turnover.PET imaging | mouse T cells | in vivo cell tracking | antibody-based cell labeling | airway DTHR

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Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer

Abstract: Due to their specific binding characteristics, the anti-PSMA mAbs 3/A12, 3/E7, and 3/F11 show great promise for diagnostic and therapeutic applications in prostate cancer.

Cited by 68 publications

References 27 publications

In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

PMPA for Nephroprotection in PSMA-Targeted Radionuclide Therapy of Prostate Cancer

⁶⁴ Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET

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Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer

Abstract: Due to their specific binding characteristics, the anti-PSMA mAbs 3/A12, 3/E7, and 3/F11 show great promise for diagnostic and therapeutic applications in prostate cancer.

Cited by 68 publications

References 27 publications

In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

PMPA for Nephroprotection in PSMA-Targeted Radionuclide Therapy of Prostate Cancer

64 Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET

Contact Info

Product

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⁶⁴ Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET