Alkaline phosphatase, placental and placental-like 2 (ALPP/ALPPL2)

Alkaline phosphatase, placental (ALPP) and placental-like 2 (ALPPL2, also known as ALPG or germ cell alkaline phosphatase) are membrane-bound, glycosylphosphatidylinositol (GPI)-anchored enzymes that belong to the alkaline phosphatase family [1, 8]. These proteins are highly homologous and are primarily expressed during embryonic development and in the placenta, with very restricted expression in normal adult tissues, such as the testis, thymus, and cervix [1, 5, 9]. However, they are frequently overexpressed in a variety of solid tumors, including ovarian, testicular, pancreatic, and non-small cell lung cancers, as well as mesothelioma [1, 2, 12]. This oncofetal expression pattern makes them attractive targets for cancer therapy, particularly for antibody-drug conjugates (ADCs) and chimeric antigen receptor (CAR) T-cell therapies [1, 3, 6]. Biologically, these enzymes function as ectonucleotidases that can hydrolyze extracellular nucleotides like ATP, ADP, and AMP, potentially contributing to an immunosuppressive tumor microenvironment through the production of adenosine [9]. Therapeutic strategies targeting ALPP/ALPPL2, such as the investigational ADC SGN-ALPV, aim to deliver potent cytotoxic agents directly to tumor cells while minimizing damage to healthy tissues [1, 11].

Other names

ALPPALPPL2ALPGPLAPGCAPPlacental alkaline phosphataseGerm cell alkaline phosphatasePlacental-like alkaline phosphatase 2

Antibody-drug conjugate (ADC) mediated cytotoxicity