Molecular constructs for treating tumors

1. A molecular construct comprising,

a pair of CH2-CH3 segments of an IgG Fc;

a peptide extension having a sequence of (G 2-4 S) 2-8 C and linked to the C-terminus of one of the pair of CH2-CH3 segments;

a coupling arm linked to the C-terminus of the peptide extension via thiol-maleimide reaction occurred therebetween;

a first pair of effector elements, wherein each effector element is a drug bundle; and

a first pair of targeting elements, wherein the targeting element is a growth factor or a peptide hormone, wherein,

the effector elements are respectively linked to the C-termini of the pair of CH2-CH3 segments, and the targeting elements are respectively linked to the N-termini of the pair of CH2-CH3 segments; and

the drug bundle comprises,

a center core that is a compound having a plurality of amine groups or a polypeptide comprising a plurality of lysine (K) residues, wherein each K residue and its next K residue are separated by a filler sequence comprising glycine (G) and serine (S) residues, and the number of K residues ranges from 2 to 15;

a plurality of linking arms, each having one terminus linked to the center core by reacting with one of the amine groups of the compound or one of the K residues, and carrying a maleimide group at the free terminus thereof; and

a plurality of molecules of, a cytotoxic drug, a toll-like receptor (TLR) agonist, or a chelator complexed with a radioactive nuclide, wherein each of the molecules is linked to the center core via connecting through the linking arm by reacting with the maleimide group, and the drug bundle is linked to the coupling arm via inverse electron demand Diels-Alder (iEDDA) reaction, strain-promoted azide-alkyne click chemistry (SPAAC) reaction, or Copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction occurred therebetween;

wherein the amino acid residue at the N- or C-terminus of the center core has an azide group or an alkyne group; or the amino acid residue at the N- or C-terminus of the center core is a cysteine residue, and the cysteine residue of the center core is linked with the coupling arm having an alkyne group, azide group, tetrazine group, or strained alkyne group at the free terminus of the coupling arm.

2. The molecular construct of claim 1 , wherein the pair of CH2-CH3 segments is derived from human γ4 or γ1 immunoglobulin.

3. The molecular construct of claim 1 , further comprising a second pair of targeting elements, wherein the second pair of targeting elements is linked, in a tandem or diabody configuration, to the N-termini of the first pair of targeting elements.

4. The molecular construct of claim 1 , wherein the cytotoxic drug is auristatin, maytansine, doxorubicin, calicheamicin, or camptothecin.

5. The molecular construct of claim 1 , wherein the TLR agonist is LPS, monophosphoryl lipid A, motolimod, imiquimod, resiquimod, gardiquimod, CpG DON, lipoteichoic acid, β-glucan, or zymosan.

6. The molecular construct of claim 1 , wherein the chelator is DOTA, NOTA, NODA, or DTPA.

7. The molecular construct of claim 1 , wherein the radioactive nuclide is 90 Y, 111 In, or 177 Lu.

8. The molecular construct of claim 1 , wherein the growth factor is epidermal growth factor (EGF), mutant EGF, epiregulin, heparin-binding epidermal growth factor (HB-EGF), VEGF-A, basic fibroblast growth factor (bFGF), or hepatocyte growth factor (HGF).

9. The molecular construct of claim 1 , wherein the hapten is dinitrophenol (DNP), trinitrophenol (TNP), dansyl, penicillin, p-aminobenzoic acid, or a polypeptide having the amino acid sequence of SEQ ID No: 20.

10. The molecular construct of claim 1 , wherein the peptide hormone is cholecystokinin (CCK), somastatin, or thyroid-stimulating hormone (TSH).

11. The molecular construct of claim 1 , wherein,

the effector element is the drug bundle comprising the plurality of molecules of the cytotoxic drug; and

the targeting element is EGF.